missense mutation

Summary

Summary: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)

Top Publications

  1. pmc A missense mutation in CRYBA4 associated with congenital cataract and microcornea
    Guangkai Zhou
    Department of Ophthalmology, Harbin Medical University The 2nd Affiliated Hospital, Harbin, Heilongjiang, China
    Mol Vis 16:1019-24. 2010
  2. pmc Predicting deleterious amino acid substitutions
    P C Ng
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Genome Res 11:863-74. 2001
  3. ncbi Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition
    Bernard Grisart
    Department of Genetics, Faculty of Veterinary Medicine, University of Liège B43, 4000 Liege, Belgium
    Genome Res 12:222-31. 2002
  4. ncbi EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy
    J Guillermo Paez
    Departments of Medical Oncology and Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 304:1497-500. 2004
  5. pmc Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle
    Miri Cohen-Zinder
    Institute of Animal Sciences, Agricultural Research Organization, Bet Dagan 50250, Israel
    Genome Res 15:936-44. 2005
  6. pmc High metastatic potential in mice inheriting a targeted p53 missense mutation
    G Liu
    Department of Molecular Genetics, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 97:4174-9. 2000
  7. pmc Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis
    Shunsuke Kato
    Department of Clinical Oncology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980 8575, Japan
    Proc Natl Acad Sci U S A 100:8424-9. 2003
  8. pmc Mutation analysis of congenital cataract in a Chinese family identified a novel missense mutation in the connexin 46 gene (GJA3)
    Zhou Zhou
    Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
    Mol Vis 16:713-9. 2010
  9. ncbi Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses
    M Hatta
    Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA
    Science 293:1840-2. 2001
  10. pmc A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy
    Umrao R Monani
    Department of Neurology, Ohio State University, Columbus, OH 43210, USA
    J Cell Biol 160:41-52. 2003

Detail Information

Publications360 found, 100 shown here

  1. pmc A missense mutation in CRYBA4 associated with congenital cataract and microcornea
    Guangkai Zhou
    Department of Ophthalmology, Harbin Medical University The 2nd Affiliated Hospital, Harbin, Heilongjiang, China
    Mol Vis 16:1019-24. 2010
    ..To identify mutations in a Chinese family with congenital cataract and microcornea...
  2. pmc Predicting deleterious amino acid substitutions
    P C Ng
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Genome Res 11:863-74. 2001
    ..may be used to identify plausible disease candidates among the SNPs that cause missense substitutions...
  3. ncbi Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition
    Bernard Grisart
    Department of Genetics, Faculty of Veterinary Medicine, University of Liège B43, 4000 Liege, Belgium
    Genome Res 12:222-31. 2002
    ....
  4. ncbi EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy
    J Guillermo Paez
    Departments of Medical Oncology and Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 304:1497-500. 2004
    ..These results suggest that EGFR mutations may predict sensitivity to gefitinib...
  5. pmc Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle
    Miri Cohen-Zinder
    Institute of Animal Sciences, Agricultural Research Organization, Bet Dagan 50250, Israel
    Genome Res 15:936-44. 2005
    ..09% fat, and 0.08% protein (F-value = 394), with partial dominance towards the 581S homozygotes. We therefore propose that Y581S in ABCG2 is the causative site for this QTL...
  6. pmc High metastatic potential in mice inheriting a targeted p53 missense mutation
    G Liu
    Department of Molecular Genetics, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 97:4174-9. 2000
    ..These data indicate clear differences between a p53 missense mutation and a null allele in tumorigenesis in vivo and suggest that the p53R172HDeltag mutant represents a gain-of-..
  7. pmc Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis
    Shunsuke Kato
    Department of Clinical Oncology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980 8575, Japan
    Proc Natl Acad Sci U S A 100:8424-9. 2003
    ..This high-resolution mutation analysis allows evaluation of previous predictions and hypotheses through interrelation of function, structure and mutation...
  8. pmc Mutation analysis of congenital cataract in a Chinese family identified a novel missense mutation in the connexin 46 gene (GJA3)
    Zhou Zhou
    Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
    Mol Vis 16:713-9. 2010
    ..To identify the genetic defects in a three-generation Chinese family with congenital nuclear cataract...
  9. ncbi Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses
    M Hatta
    Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA
    Science 293:1840-2. 2001
    ..Moreover, high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection...
  10. pmc A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy
    Umrao R Monani
    Department of Neurology, Ohio State University, Columbus, OH 43210, USA
    J Cell Biol 160:41-52. 2003
    ..Our mild SMA mice will be useful in (a) determining the effect of missense mutations in vivo and in motor neurons and (b) testing potential therapies in SMA...
  11. pmc A missense mutation in desmin tail domain linked to human dilated cardiomyopathy promotes cleavage of the head domain and abolishes its Z-disc localization
    Manolis Mavroidis
    Cell Biology Division, Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens, Greece
    FASEB J 22:3318-27. 2008
    A missense mutation (Ile 451 to Met) at the tail domain of the muscle-specific intermediate filament protein desmin has been suggested to be a genetic cause of dilated cardiomyopathy...
  12. ncbi HCCS loss-of-function missense mutation in a female with bilateral microphthalmia and sclerocornea: a novel gene for severe ocular malformations?
    Isabella Wimplinger
    Institut fur Humangenetik, Universitatsklinikum Hamburg Eppendorf, Hamburg, Germany
    Mol Vis 13:1475-82. 2007
    ..In addition, we investigated the impact of the p.E159K missense mutation on sorting of HCCS to mitochondria and its functional integrity.
  13. pmc Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene
    Doreen Becker
    Institute of Genetics, Vetsuisse Faculty, University of Berne, Berne, Switzerland
    PLoS ONE 5:e8689. 2010
    ..Here we show that the ovine microphthalmia phenotype is perfectly associated with a missense mutation (c.338G>C, p.R113P) in the evolutionary conserved homeodomain of PITX3...
  14. pmc Most rare missense alleles are deleterious in humans: implications for complex disease and association studies
    Gregory V Kryukov
    Division of Genetics, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02125, USA
    Am J Hum Genet 80:727-39. 2007
    ..Our results provide a justification for these types of candidate-gene (pathway) association studies and imply that mutation-selection balance may be a feasible evolutionary mechanism underlying some common diseases...
  15. pmc Missense mutation in the USH2A gene: association with recessive retinitis pigmentosa without hearing loss
    C Rivolta
    Ocular Molecular Genetics Institute and the Berman Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, 02114, USA
    Am J Hum Genet 66:1975-8. 2000
    ..Here, we report Cys759Phe, a novel missense mutation in this gene that changes an amino-acid residue within the fifth laminin-epidermal growth factor-like domain ..
  16. ncbi Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3
    I Sadaf Farooqi
    University Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge CB2 2XY, United Kingdom
    J Clin Endocrinol Metab 92:3369-73. 2007
    ..To date, only two unrelated subjects with this disorder have been reported...
  17. ncbi The nonsense-mediated decay RNA surveillance pathway
    Yao Fu Chang
    Department of Biochemistry and Molecular Biology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Annu Rev Biochem 76:51-74. 2007
    ....
  18. ncbi Extreme variability of phenotype in patients with an identical missense mutation in the lamin A/C gene: from congenital onset with severe phenotype to milder classic Emery-Dreifuss variant
    Eugenio Mercuri
    Dubowitz Neuromuscular Centre, Hammersmith Hospital Imperial College, London, England
    Arch Neurol 61:690-4. 2004
    ..Mutations of the LMNA gene, encoding the nuclear envelope proteins lamins A and C, have been associated with 7 distinct pathologic conditions...
  19. ncbi Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa
    Bart Loeys
    Center for Medical Genetics, Ghent University Hospital, Belgium
    Hum Mol Genet 11:2113-8. 2002
    ..Turkish family with four patients affected by AR cutis laxa type I demonstrated the presence of a homozygous missense mutation (T998C) in the FBLN5 gene resulting in a serine-to-proline (S227P) substitution in the fourth calcium-..
  20. ncbi A missense mutation in the non-neural G-protein alpha-subunit isoforms modulates susceptibility to obesity
    M L Kelly
    MRC Harwell, Metabolism and Inflammation Section, Diabetes Group, Harwell Science and Innovation Campus, Oxfordshire, UK
    Int J Obes (Lond) 33:507-18. 2009
    ..The aim of this study was therefore to determine the metabolic phenotypes of Oed and Sml mice, and to correlate phenotypes with affected transcripts...
  21. ncbi Structural and functional characteristics of the Val44Met insulin-like growth factor I missense mutation: correlation with effects on growth and development
    Adam Denley
    School of Molecular and Biomedical Science, University of Adelaide, Adelaide, 5005 South Australia
    Mol Endocrinol 19:711-21. 2005
    We have previously described the phenotype resulting from a missense mutation in the IGF-I gene, which leads to expression of IGF-I with a methionine instead of a valine at position 44 (Val44Met IGF-I)...
  22. pmc A missense mutation in the Arabidopsis COPII coat protein Sec24A induces the formation of clusters of the endoplasmic reticulum and Golgi apparatus
    Carmen Faso
    Department of Energy, Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA
    Plant Cell 21:3655-71. 2009
    ..These results produce important insights into the functional diversification of plant COPII coat components and the role of these proteins in maintaining the dynamic identity of organelles of the early plant secretory pathway...
  23. ncbi Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation
    Barbara Plaimauer
    Baxter BioScience, Department of Discovery Research, Vienna, Austria
    Blood 107:118-25. 2006
    ..the homozygous presence of 4 single nucleotide polymorphisms (SNPs) (R7W, Q448E, P618A, A732V) and a rare missense mutation (R1336W)...
  24. ncbi X-linked idiopathic infantile nystagmus associated with a missense mutation in FRMD7
    Alan Shiels
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 63110, USA
    Mol Vis 13:2233-41. 2007
    ..Here we map and identify the genetic mutation underlying X-linked idiopathic infantile nystagmus (XL-IIN) segregating in two Caucasian-American families...
  25. ncbi Lipid rafts mediate the synaptic localization of alpha-synuclein
    Doris L Fortin
    Department of Neurology, Graduate Programs in Biomedical Sciences, Cell Biology and Neuroscience, University of California San Francisco School of Medicine, San Francisco, California 94143 2140, USA
    J Neurosci 24:6715-23. 2004
    ....
  26. pmc Testing computational prediction of missense mutation phenotypes: functional characterization of 204 mutations of human cystathionine beta synthase
    Qiong Wei
    Program in Molecular and Translational Medicine, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA
    Proteins 78:2058-74. 2010
    ....
  27. ncbi A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects
    Dganit Dinour
    Department of Nephrology and Hypertension, Chaim Sheba Medical Center, Tel Hashomer, and Tel Aviv University, 52621 Israel
    J Biol Chem 279:52238-46. 2004
    ..1999) Nat. Genet. 23, 264-266). We have identified and functionally characterized a novel, homozygous, missense mutation (S427L) in NBCe1, also resulting in pRTA and similar eye defects without mental retardation...
  28. pmc Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals
    M Matrosovich
    Department of Virology and Molecular Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, Russia
    J Virol 74:8502-12. 2000
    ....
  29. pmc Classification of BRCA1 missense variants of unknown clinical significance
    C M Phelan
    H Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA
    J Med Genet 42:138-46. 2005
    ..Classification of missense variants into deleterious/high risk or neutral/low clinical significance is essential to identify individuals at risk...
  30. ncbi Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/cardiomyopathy
    Zhao Yang
    Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    Circ Res 99:646-55. 2006
    ..These data suggest DSP expression in cardiomyocytes is crucial for maintaining cardiac tissue integrity, and DSP abnormalities result in ARVD/C by cardiomyocyte death, changes in lipid metabolism, and defects in cardiac development...
  31. pmc Determination of cancer risk associated with germ line BRCA1 missense variants by functional analysis
    Marcelo A Carvalho
    Risk Assessment, Detection, and Intervention Program, H Lee Moffitt Cancer Center, University of South Florida College of Medicine, 12902 Magnolia Drive, Tampa, FL 33612, USA
    Cancer Res 67:1494-501. 2007
    ..These results bring functional assays for BRCA1 closer to clinical applicability...
  32. ncbi Comparative full genome analysis revealed E1: A226V shift in 2007 Indian Chikungunya virus isolates
    S R Santhosh
    Division of Virology, Defence R and D Establishment, Gwalior, MP, India
    Virus Res 135:36-41. 2008
    ....
  33. pmc Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum
    Ellen G Pfendner
    GeneDx Inc, 207 Perry Parkway, Gaithersburg, Maryland 20877, USA
    J Med Genet 44:621-8. 2007
    ..It is caused by mutations in the ABCC6 (ATP binding cassette family C member 6) gene, which encodes MRP6 (multidrug resistance-associated protein 6)...
  34. pmc A new missense mutation in the L ferritin coding sequence associated with elevated levels of glycosylated ferritin in serum and absence of iron overload
    Caroline Kannengiesser
    AP HP, Service de Génétique et Biochimie hormonale, Hopital Bichat Claude Bernard, Paris, France
    Haematologica 94:335-9. 2009
    ..Genetic causes of hyperferritinemia associated to early cataract include mutations in the iron responsive element in the 5' untranslated region of the L ferritin mRNA, responsible for the hereditary hyperferritinemia cataract syndrome...
  35. pmc 250K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies
    Andrew J Dunbar
    Department of Hematologic Oncology and Blood Disorders, Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio 44195, USA
    Cancer Res 68:10349-57. 2008
    ..Acquired mutations of c-Cbl E3 ubiquitin ligase may explain the pathogenesis of a clonal process in a subset of MDS/MPD, including CMML...
  36. ncbi A Gly482Ser missense mutation in the peroxisome proliferator-activated receptor gamma coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians
    Yunhua Li Muller
    Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease NIH, 4212 N 16th Street, Phoenix, AZ 85016, USA
    Diabetes 52:895-8. 2003
    ..These data indicate that the Gly482Ser missense polymorphism in PGC-1 has metabolic consequences on lipid metabolism that could influence insulin secretion...
  37. pmc Understanding missense mutations in the BRCA1 gene: an evolutionary approach
    Melissa A Fleming
    Divisions of Clinical Research and Human Biology, and Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
    Proc Natl Acad Sci U S A 100:1151-6. 2003
    ..Investigation of the functional role of missense changes in breast-cancer susceptibility should focus on 38 missense changes in conserved and 3 in rapidly evolving regions of exon 11...
  38. ncbi A novel missense mutation of the EDA gene in a Mongolian family with congenital hypodontia
    Ran Tao
    Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, 200031, Shanghai, China
    J Hum Genet 51:498-502. 2006
    ..We successfully mapped the affected locus to chromosome Xq12-q13.1, and then found a novel missense mutation, c.193C>G, in the ectodysplasin A (EDA) gene in all affected males and carrier females...
  39. ncbi A missense mutation in the transmembrane domain of CESA4 affects protein abundance in the plasma membrane and results in abnormal cell wall biosynthesis in rice
    Baocai Zhang
    National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101 Beijing, China
    Plant Mol Biol 71:509-24. 2009
    ..Map-based cloning revealed that all the mutant phenotypes result from a missense mutation in OsCESA4 (G858R), a highly conserved residue at the end of the fifth transmembrane domain...
  40. ncbi Omani-type spondyloepiphyseal dysplasia with cardiac involvement caused by a missense mutation in CHST3
    B Tuysuz
    Department of Pediatric Genetics, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
    Clin Genet 75:375-83. 2009
    ..in CHST3, the gene encoding for the chondroitin 6-O-sulfotransferase-1 (C6ST-1), revealed a homozygous missense mutation (T141M) in exon 3 in all three affected members of the family...
  41. ncbi Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia
    Sonny O Ang
    Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA
    Nat Genet 32:614-21. 2002
    ..with von Hippel-Lindau syndrome, VHL, maps to this region, and homozygosity with respect to a C-->T missense mutation in VHL, causing an arginine-to-tryptophan change at amino-acid residue 200 (Arg200Trp), was identified in ..
  42. ncbi Aberrant splicing induced by missense mutations in BRCA1: clues from a humanized mouse model
    Yongping Yang
    Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute at Frederick, 1050 Boyles Street, Frederick, MD 21702, USA
    Hum Mol Genet 12:2121-31. 2003
    ..Using a humanized mouse model we demonstrate that this missense mutation actually results in a functionally null protein...
  43. pmc A missense mutation in SLC33A1, which encodes the acetyl-CoA transporter, causes autosomal-dominant spastic paraplegia (SPG42)
    Pengfei Lin
    Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Medical Genetics, Shandong University School of Medicine, Shandong, China
    Am J Hum Genet 83:752-9. 2008
    ..Screening of candidate genes revealed that the HSP is caused by a missense mutation in the gene for acetyl-CoA transporter (SLC33A1)...
  44. pmc Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis
    Nicola J Rutherford
    Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America
    PLoS Genet 4:e1000193. 2008
    ....
  45. ncbi Early onset, non fluctuating spinocerebellar ataxia and a novel missense mutation in CACNA1A gene
    Alessandra Tonelli
    IRCCS Eugenio Medea, Via Don Luigi Monza 20, Bosisio Parini, Lecco, Italy
    J Neurol Sci 241:13-7. 2006
    ..Complete loss of P/Q calcium channel activity caused by a CACNA1A missense mutation carried by patients with episodic ataxia type 2...
  46. ncbi A recurrent ITGA9 missense mutation in human fetuses with severe chylothorax: possible correlation with poor response to fetal therapy
    Gwo Chin Ma
    Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan
    Prenat Diagn 28:1057-63. 2008
    ..To assess the possible correlations between the reported candidate genes (VEGFR3, FOXC2, ITGA9 and ITGB1) and the clinical response in fetuses with severe congenital chylothorax (CC) treated by prenatal OK-432 pleurodesis...
  47. ncbi Severe cardiac phenotype with right ventricular predominance in a large cohort of patients with a single missense mutation in the DES gene
    J Peter van Tintelen
    Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Heart Rhythm 6:1574-83. 2009
    ..Mutations in the gene encoding desmin (DES), a major intermediate filament protein, can underlie this phenotype...
  48. ncbi A shared Asian origin of the triple-mutant dhfr allele in Plasmodium falciparum from sites across Africa
    Oumou Maïga
    Universite Paris Descartes, Paris, France
    J Infect Dis 196:165-72. 2007
    ..A predominant haplotype associated with the N51I+C59R+S108N triple-mutant dhfr allele has been reported recently in 4 African countries. A more comprehensive picture of the evolution of this mutant allele in Africa is lacking...
  49. pmc Assessing the evolutionary impact of amino acid mutations in the human genome
    Adam R Boyko
    Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA
    PLoS Genet 4:e1000083. 2008
    ....
  50. ncbi A novel missense mutation in the gene for gap-junction protein alpha3 (GJA3) associated with autosomal dominant "nuclear punctate" cataracts linked to chromosome 13q
    Thomas M Bennett
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 63110, USA
    Mol Vis 10:376-82. 2004
    ..The purpose of this study was to map and identify the mutation underlying autosomal dominant nuclear punctate cataracts segregating in a six generation Caucasian pedigree...
  51. pmc A homozygous missense mutation in the IRBP gene (RBP3) associated with autosomal recessive retinitis pigmentosa
    Anneke I den Hollander
    Berman Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Massachusetts 02114, USA
    Invest Ophthalmol Vis Sci 50:1864-72. 2009
    ..This study was performed to determine whether mutations in the IRBP gene (RBP3) are associated with photoreceptor degeneration...
  52. ncbi Structure-based assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition
    Nebojsa Mirkovic
    Laboratory of Molecular Biophysics, Pels Family Center for Biochemistry and Structural Biology, Rockefeller University, New York, New York, USA
    Cancer Res 64:3790-7. 2004
    ..Next, structure-based rules for predicting functional consequences of a given missense mutation were applied to 57 germ-line BRCA1 variants of unknown cancer association...
  53. ncbi Defective membrane interactions of familial Parkinson's disease mutant A30P alpha-synuclein
    Euijung Jo
    Centre for Research in Neurodegenerative Diseases, 6 Queen s Park Crescent West, Toronto, Ontario, M5S 3H2, Canada
    J Mol Biol 315:799-807. 2002
    ..With these observations, we suggest that the A53T and A30P mutants may have different physiological consequences in vivo and could possibly contribute to early onset Parkinson's disease via unique mechanisms...
  54. pmc Thermostability/infectivity defect caused by deletion of the core protein V gene in human adenovirus type 5 is rescued by thermo-selectable mutations in the core protein X precursor
    Hideyo Ugai
    Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    J Mol Biol 366:1142-60. 2007
    ..The possible mechanism of the observed genetic suppression is discussed...
  55. pmc Reduced susceptibility to polyenes associated with a missense mutation in the ERG6 gene in a clinical isolate of Candida glabrata with pseudohyphal growth
    Patrick Vandeputte
    Groupe d Etude des Interactions Hôte Parasite, UPRES EA 3142, Laboratoire de Parasitologie Mycologie, Centre Hospitalier Universitaire, 4 rue Larrey, 49933 Angers Cedex 9, France
    Antimicrob Agents Chemother 51:982-90. 2007
    ..Sequencing of CgERG11, CgERG6, CgERG5, and CgERG4 genes revealed exclusively a unique missense mutation in CgERG6 leading to the substitution of a cysteine by a phenylalanine in the corresponding protein...
  56. ncbi A missense mutation (c.184C>T) in ovine CLN6 causes neuronal ceroid lipofuscinosis in Merino sheep whereas affected South Hampshire sheep have reduced levels of CLN6 mRNA
    Imke Tammen
    Centre for Advanced Technologies in Animal Genetics and Reproduction REPROGEN, Faculty of Veterinary Science, The University of Sydney, PMB3, Camden, NSW, Australia
    Biochim Biophys Acta 1762:898-905. 2006
    ..184C>T mutation but show reduced expression of CLN6 mRNA in a range of tissues as determined by real-time PCR. Lack of linkage precludes CLN6 as a candidate for NCL in Borderdale sheep...
  57. pmc VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P(2) in yeast and mouse
    Natsuko Jin
    Department of Cell and Developmental Biology and Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 2216, USA
    EMBO J 27:3221-34. 2008
    ..We also report that the mouse mutant ingls (infantile gliosis) results from a missense mutation in Vac14 that prevents the association of Vac14 with Fab1, generating a partial complex...
  58. pmc Functional assays for BRCA1 and BRCA2
    Marcelo A Carvalho
    Department of Risk Assessment, Detection, and Intervention, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
    Int J Biochem Cell Biol 39:298-310. 2007
    ..Here we advocate the use of functional assays to complement genetic data in the analysis of unclassified missense mutations and propose a set of standards to conduct and interpret these assays...
  59. ncbi ATM mutations are associated with inactivation of the ARF-TP53 tumor suppressor pathway in diffuse large B-cell lymphoma
    Kirsten Grønbaek
    Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark
    Blood 100:1430-7. 2002
    ..Our data suggest that ATM mutations contribute to the development of DLBCL, and that ATM and the ARF-p53 tumor suppressor pathway may cooperate in the pathogenesis of this malignancy...
  60. pmc Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation
    V Abkevich
    Myriad Genetics, Inc, Salt Lake City, UT, 84108, USA
    J Med Genet 41:492-507. 2004
    ..Before this study, only 21 of these missense changes were classified as deleterious or suspected deleterious and 14 as neutral or of little clinical significance...
  61. pmc A missense mutation in LIM2 causes autosomal recessive congenital cataract
    Surya Prakash G Ponnam
    Kallam Anji Reddy Molecular Genetics Laboratory, Hyderabad Eye Research Foundation, LV Prasad Eye Institute, Hyderabad, India
    Mol Vis 14:1204-8. 2008
    ..To identify mutations in the LIM2 gene in families with hereditary congenital or juvenile-onset cataract...
  62. ncbi Distinct effects of single amino-acid changes to tuberin on the function of the tuberin-hamartin complex
    Mark Nellist
    Department of Clinical Genetics, Erasmus MC, 3015 GE Rotterdam, The Netherlands
    Eur J Hum Genet 13:59-68. 2005
    ..Here, we investigate how these mutations affect the role of tuberin in the control of signal transduction through mTOR. Our data indicate that specific amino-acid substitutions have distinct effects on tuberin function...
  63. pmc A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export
    Chen Zhang
    Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, California 94304, USA
    J Neurosci 29:10843-54. 2009
    ..Viewed together, these observations suggest that a point mutation in NL4 can cause ASD by a loss-of-function mechanism...
  64. ncbi Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA
    N M Makridakis
    Department of Biochemistry and Molecular Biology and Institute for Genetic Medicine, University of Southern California School of Medicine, 90033, USA
    Lancet 354:975-8. 1999
    ..It is an androgen-dependent cancer, and androgens have been proposed as having a substantial role in predisposition to the disease. Thus, variations in androgen metabolism genes may affect risk of this disease...
  65. ncbi A new missense mutation in the leptin gene causes mild obesity and hypogonadism without affecting T cell responsiveness
    Pamela Fischer-Posovszky
    Division of Pediatric Endocrinology and Diabetes, University of Ulm, Eythstrasse 24, 89075 Ulm, Germany
    J Clin Endocrinol Metab 95:2836-40. 2010
    ..So far, only three homozygous mutations in the leptin gene in a total of 13 individuals have been found leading to a phenotype of extreme obesity with marked hyperphagia and impaired immune function...
  66. ncbi Hypogonadotropic hypogonadism due to a novel missense mutation in the first extracellular loop of the neurokinin B receptor
    Tulay Guran
    Pediatric Endocrinology, Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey
    J Clin Endocrinol Metab 94:3633-9. 2009
    ..We have recently reported two mutations in transmembrane segments of the receptor and a missense mutation in NKB in patients with normosmic isolated hypogonadotropic hypogonadism (nIHH).
  67. ncbi A novel missense mutation in the transmembrane domain of neuregulin 1 is associated with schizophrenia
    Consuelo Walss-Bass
    Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas, USA
    Biol Psychiatry 60:548-53. 2006
    ..The neuregulin 1 gene is among the few candidate genes to have been implicated in schizophrenia susceptibility in several populations. However, no causal mutations within this gene have been identified...
  68. ncbi SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification
    G J McKenzie
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030 3411, USA
    Mol Cell 7:571-9. 2001
    ..We show that pol IV, together with the major replicase, pol III, can account for all adaptive point mutations at lac. The results identify a role for pol IV in inducible genetic change...
  69. ncbi Frataxin gene point mutations in Italian Friedreich ataxia patients
    Cinzia Gellera
    UO Biochimica e Genetica, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy
    Neurogenetics 8:289-99. 2007
    ..01) correlation was observed between the size of GAA expansion and the age at onset, thus lending support to the hypothesis that the residual function of frataxin in patients' cells derive exclusively from the expanded allele...
  70. pmc Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene
    Nancy D Merner
    Faculty of Medicine, Memorial University, St John s, Newfoundland and Labrador A1B 3V6, Canada
    Am J Hum Genet 82:809-21. 2008
    ....
  71. pmc X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment
    Leanne M Dibbens
    Department of Genetic Medicine, Level 9 Rieger Building, Women s and Children s Hospital, 72 King William Road, North Adelaide, South Australia 5006, Australia
    Nat Genet 40:776-81. 2008
    ..PCDH19 is expressed in developing brains of human and mouse and is the first member of the cadherin superfamily to be directly implicated in epilepsy or mental retardation...
  72. pmc An integrated genomic analysis of human glioblastoma multiforme
    D Williams Parsons
    Ludwig Center for Cancer Genetics and Therapeutics, and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 321:1807-12. 2008
    ..These studies demonstrate the value of unbiased genomic analyses in the characterization of human brain cancer and identify a potentially useful genetic alteration for the classification and targeted therapy of GBMs...
  73. pmc Mutations in TRPM1 are a common cause of complete congenital stationary night blindness
    Maria M van Genderen
    Bartiméus, Institute for the Visually Impaired, 3702 AD Zeist, The Netherlands
    Am J Hum Genet 85:730-6. 2009
    ..These results add to the growing importance of the diverse group of TRP channels in human disease and also provide new insights into retinal circuitry...
  74. ncbi Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele
    Johannes Bange
    Department of Molecular Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    Cancer Res 62:840-7. 2002
    ..Our results support the conclusion that the FGFR4 Arg(388) allele represents a determinant that is innocuous in healthy individuals but predisposes cancer patients for significantly accelerated disease progression...
  75. ncbi SNPs, protein structure, and disease
    Z Wang
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA
    Hum Mutat 17:263-70. 2001
    ..In sharp contrast, over 70% of the population set are found to be neutral. The remaining 30% are potentially involved in polygenic disease...
  76. ncbi Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype--phenotype correlation
    E De Baere
    Department of Medical Genetics, Ghent University Hospital, B 9000 Ghent, Belgium
    Hum Mol Genet 10:1591-600. 2001
    ..Furthermore, we propose that in a fraction of the BPES patients the genetic defect does not reside within the coding region of the FOXL2 gene and may be caused by a position effect...
  77. pmc Pseudoxanthoma elasticum: a clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations
    N Chassaing
    Department of Medical Genetics, INSERM U563, Purpan Hospital, Toulouse, France
    J Med Genet 42:881-92. 2005
    ....
  78. pmc Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive osteogenesis imperfecta
    Helena E Christiansen
    Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA
    Am J Hum Genet 86:389-98. 2010
    ..We have identified an autosomal-recessive missense mutation (c.233T>C, p...
  79. pmc DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4)
    Ying Zhang Chen
    Division of Genetics and Developmental Medicine, University of Washington, Seattle, WA 98195, USA
    Am J Hum Genet 74:1128-35. 2004
    ..These observations of ALS4 suggest that mutations in SETX may cause neuronal degeneration through dysfunction of the helicase activity or other steps in RNA processing...
  80. pmc Analyses of the effects that disease-causing missense mutations have on the structure and function of the winged-helix protein FOXC1
    R A Saleem
    Department of Medical Genetics, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada
    Am J Hum Genet 68:627-41. 2001
    ..In addition, these findings demonstrate that reduced stability, DNA binding, or transactivation, all causing a decrease in the ability of FOXC1 to transactivate genes, can underlie AR malformations...
  81. ncbi Contributions of ATM mutations to familial breast and ovarian cancer
    Yvonne R Thorstenson
    Stanford Genome Technology Center, Palo Alto, California 94304 1103, USA
    Cancer Res 63:3325-33. 2003
    ..This study indicates that there is a significant prevalence of ATM mutations in breast and ovarian cancer families and adds to a growing body of evidence that ATM mutations confer increased susceptibility to breast cancer...
  82. ncbi Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas
    D Cappellen
    Laboratoire de Morphogenèse Cellulaire et Progression Tumorale, UMR 144, Centre National de la Recherche Scientifique, Institut Curie, Section de Recherche, 26 Rue d Ulm, 75248 Paris Cedex 05, France
    Nat Genet 23:18-20. 1999
  83. ncbi New type of disease causing mutations: the example of the composite exonic regulatory elements of splicing in CFTR exon 12
    Franco Pagani
    International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste 34012, Italy
    Hum Mol Genet 12:1111-20. 2003
    ..Hence, appropriate functional splicing assays should be included in genotype screenings to distinguish between polymorphisms and pathogenic mutations...
  84. pmc A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice
    Eileen Workman
    Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210, USA
    Hum Mol Genet 18:2215-29. 2009
    ..Also, the SMN(A2G) and SMN(A111G) alleles in vivo did not complement each other leading to the possibility that these mutations could affect the same function...
  85. ncbi The R71G BRCA1 is a founder Spanish mutation and leads to aberrant splicing of the transcript
    A Vega
    Unidad de Medicina Molecular, INGO-SERGAS, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
    Hum Mutat 17:520-1. 2001
    ..screening in familial breast cancer carried out in different centres in Spain, France, and United Kingdom, a missense mutation 330A>G which results in a Arg to Gly change at codon 71 (R71G) was independently identified in 6 families, ..
  86. ncbi Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking
    P H Dixon
    Division of Medicine, Imperial College School of Medicine, London, UK
    Hum Mol Genet 9:1209-17. 2000
    ..Fluorescence activated cell sorting (FACS) and western analysis indicated that this missense mutation causes disruption of protein trafficking with a subsequent lack of functional protein at the cell surface...
  87. pmc Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) are associated with 46,XY disorders of sex development with normal adrenal function
    Lin Lin
    Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, UCL Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom
    J Clin Endocrinol Metab 92:991-9. 2007
    ..Consistent with the murine phenotype, human mutations in SF1 were described initially in two 46,XY individuals with female external genitalia, Müllerian structures (uterus), and primary adrenal failure...
  88. pmc The novel mouse mutation Oblivion inactivates the PMCA2 pump and causes progressive hearing loss
    Sarah L Spiden
    Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, UK
    PLoS Genet 4:e1000238. 2008
    ..We mapped the mutation to Chromosome 6. Mutation analysis of Atp2b2 showed a missense mutation (2630C-->T) in exon 15, causing a serine to phenylalanine substitution (S877F) in transmembrane domain 6 ..
  89. ncbi Neurological aspects of hyperinsulinism-hyperammonaemia syndrome
    Nadia Bahi-Buisson
    Department of Paediatric Neurology and Metabolic Diseases, Necker Children s Hospital, Paris V University, Paris, France
    Dev Med Child Neurol 50:945-9. 2008
    ..Our data demonstrate that neurological disorders in HHS are more frequent than previously thought and might suggest that mutations in the GTP binding site of GDH could be associated with more frequent epilepsy...
  90. ncbi Genetics and phenotypes of RPE65 mutations in inherited retinal degeneration
    D A Thompson
    Departments of Ophthalmology and Visual Sciences and Biological Chemistry, University of Michigan Medical School, Ann Arbor, USA
    Invest Ophthalmol Vis Sci 41:4293-9. 2000
    ..To characterize the spectrum of RPE65 mutations present in 453 patients with retinal dystrophy with an interest in understanding the range of functional deficits attributable to sequence variants in this gene...
  91. pmc A missense mutation in the bovine SLC35A3 gene, encoding a UDP-N-acetylglucosamine transporter, causes complex vertebral malformation
    Bo Thomsen
    Department of Genetics and Biotechnology, Danish Institute of Agricultural Sciences, DK 8830 Tjele, Denmark
    Genome Res 16:97-105. 2006
    ....
  92. pmc A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum
    O Le Saux
    Pacific Biomedical Research Center, University of Hawai i, Honolulu, HI 96822, USA
    Am J Hum Genet 69:749-64. 2001
    ..We discuss the potential structural and functional significance of this mutation pattern within the context of the complex relationship between the PXE phenotype and the function of ABCC6...
  93. pmc Accurate prediction of the functional significance of single nucleotide polymorphisms and mutations in the ABCA1 gene
    Liam R Brunham
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia
    PLoS Genet 1:e83. 2005
    ....
  94. ncbi Metabolic consequences of a novel missense mutation of the mtDNA CO I gene
    Dmitry A Varlamov
    Department of Epileptology, University of Bonn Medical Center, Sigmund Freud Strasse 25, D 53105 Bonn, Germany
    Hum Mol Genet 11:1797-805. 2002
    We have identified a novel heteroplasmic C6489A missense mutation in the mitochondrial DNA (mtDNA) CO I gene encoding the cytochrome c oxidase (COX) subunit I in a 17-year-old girl with epilepsia partialis continua...
  95. pmc Missense mutation in the alternative splice region of the PAX6 gene in eye anomalies
    N Azuma
    Department of Ophthalmology, National Children s Hospital, Tokyo 154 8509, Japan
    Am J Hum Genet 65:656-63. 1999
    ..Thus, exon 5a appears to function as a molecular switch that specifies target genes. We ascertained a novel missense mutation in four pedigrees with Peters anomaly, congenital cataract, Axenfeldt anomaly, and/or foveal hypoplasia, ..
  96. ncbi Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene
    Y Kaplan
    Department of Neurology, Gaziosmanpasa University, Medical Faculty, Tokat, Turkey
    Br J Ophthalmol 92:135-41. 2008
    ..This study aimed to identify the underlying genetic defect of a large Turkish X linked nystagmus (NYS) family...
  97. ncbi Brittle cornea syndrome associated with a missense mutation in the zinc-finger 469 gene
    Anne E Christensen
    Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
    Invest Ophthalmol Vis Sci 51:47-52. 2010
    ..To investigate the diverse clinical manifestations, identify the causative mutation and explain the association with red hair in a family with brittle cornea syndrome (BCS)...
  98. ncbi Functional study in a yeast model of a novel succinate dehydrogenase subunit B gene germline missense mutation (C191Y) diagnosed in a patient affected by a glomus tumor
    Paola Goffrini
    Department of Genetics, Biology of Microorganisms, Anthropology and Evolution, University of Parma, Parma, Italy
    Hum Mol Genet 18:1860-8. 2009
    ..We report a novel germline missense SDHB mutation (C191Y) in a patient affected by a glomus tumor. The missense mutation hits an amino acid residue conserved from mammals to the yeast Saccharomyces cerevisiae...
  99. ncbi R561C missense mutation in the SMARCAL1 gene associated with mild Schimke immuno-osseous dysplasia
    Arend Bokenkamp
    Department of Pediatrics, Vrije University Medical Center, Amsterdam, The Netherlands
    Pediatr Nephrol 20:1724-8. 2005
    ..The novel R561C missense mutation in our patient with mild SIOD is additional evidence for the genotype-phenotype correlation reported for ..
  100. pmc Neuroferritinopathy: missense mutation in FTL causing early-onset bilateral pallidal involvement
    P Maciel
    Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, 4710 057 Braga, Portugal
    Neurology 65:603-5. 2005
    The authors identified a missense mutation in the FTL gene (474G>A; A96T) in a 19-year-old man with parkinsonism, ataxia, corticospinal signs, mild nonprogressive cognitive deficit, and episodic psychosis...
  101. ncbi Mutations of the human PTEN gene
    D Bonneau
    Department of Medical Genetics, University of Poitiers, Poitiers, France
    Hum Mutat 16:109-22. 2000
    ..A mutagenesis by insertion-deletion in repetitive elements is however specifically observed in endometrial carcinomas...

Research Grants63

  1. GENETIC MODULATION OF CBS TO LOWER PLASMA HOMOCYSTEINE
    Warren Kruger; Fiscal Year: 2009
    ..mice will be characterized, one with a deletion in the regulatory domain of CBS and the other with a missense mutation in this domain...
  2. Model of Timothy Syndrome to Screen Drugs with Induced Pluripotent Stem Cells
    Masayuki Yazawa; Fiscal Year: 2013
    ..Here I propose to study a missense mutation in the L-type Ca2+ channel, CaV1...
  3. Model of Timothy Syndrome to Screen Drugs with Induced Pluripotent Stem Cells
    Masayuki Yazawa; Fiscal Year: 2013
    ..Here I propose to study a missense mutation in the L-type Ca2+ channel, CaV1...
  4. High-affinity RNA targets of Survival Motor Neuron Protein
    Ravindra N Singh; Fiscal Year: 2013
    ..A single missense mutation (E134K) in tudor domain of SMN has been also linked to SMA...
  5. Analysis of the tumor suppressor gene Tsc1 in motor neuron patterning
    Onanong Chivatakarn; Fiscal Year: 2013
    ..The MN pathfinding defects in a mouse mutant called Greenlight (GrL) are caused by a missense mutation in the tuberous sclerosis complex 1 (TSC1) gene...
  6. Genetics of Age-Related Hearing Loss
    Kenneth R Johnson; Fiscal Year: 2013
    ..We previously showed that a missense mutation of fascin 2 (FSCN2), an actin bundling protein of hair cell stereocilia, underlies ahl8, a locus on distal ..
  7. Clinical trial of self complementary AAV8-mediated gene transfer for hemophilia B
    Andrew M Davidoff; Fiscal Year: 2013
    ..adults (greater than or equal to 18 years of age) with a confirmed diagnosis of severe HB resulting from a missense mutation in the hFIX gene...
  8. Understanding the Role of COMT Variants in Sensorimotor Gating
    XIANJIN ZHOU; Fiscal Year: 2010
    A single nucleotide polymorphism (SNP), causing a missense mutation of codon 158 Valine to Methionine in the coding region (termed val158met), exists in the human catechol-o-methyltransferase (COMT) gene...
  9. Mitochondrial Inborn Errors in Metabolism
    Douglas C Wallace; Fiscal Year: 2013
    ..interactions in generating the variable penetrance of LHON by combining the ND6 P25L mtDNA with a knockin missense mutation in an X- linked complex I gene and with an inducible mitochondrially-targeted catalase (mCAT)...
  10. Molecular Pathogenesis of Coenzyme Q10 Deficiency
    Michio Hirano; Fiscal Year: 2012
    ..CoQ10-deficiency;in two siblings with the infantile form of CoQ10 deficiency, we identified a homozygous missense mutation in the COQ2 gene which encodes para-hydroxybenzoate-polyprenyl transferase, the enzyme responsible for the ..
  11. Novel Immunodeficiency caused by TFRC Mutation
    RAIF SALIM GEHA; Fiscal Year: 2013
    ..All 14 affected members of a consanguineous Kuwaiti family were homozygous for a missense mutation in TFRC, which substitutes the tyrosine residue in the TfR1 internalization signal motif 20YTRF23 with ..
  12. Excitability mechanisms of neurocardiac regulation
    ALBERT E GLASSCOCK; Fiscal Year: 2012
    ..model, which exhibits cardiac defects despite minimal cardiac expression;and 2) a Kcnq1 potassium channel missense mutation mouse model, which exhibits cardiac defects associated with co-expression in brain and heart...
  13. Therapeutic Development for Amyotrophic Lateral Sclerosis in a Canine Model
    JOAN RIPLEY COATES; Fiscal Year: 2013
    ..Recently, we found that an E40K missense mutation in SOD1 underlies most cases of canine DM...
  14. Serum Biomarkers Associated With Phenotypic Expression of Hemochromatosis.
    Kris Kowdley; Fiscal Year: 2013
    ..Nearly all cases of hemochromatosis are due to a homozygous missense mutation in the HFE gene that changes amino acid residue 282 from a cysteine to a tyrosine (C282Y)...
  15. Determining the Function of PNPLA3 Utilizing Metabolomics and Stable Isotope Labe
    MATTHEW ALVIN MITSCHE; Fiscal Year: 2013
    ..was first implicated in the metabolism of hepatic triacylglycerides (TAGs) when our lab found that a missense mutation that substitutes isoleucine at position 148 with methionine (I148M) was associated with non-alcoholic fatty ..
  16. Molecular Mechanisms of IDH1-mediated Gliomagenesis
    Ingo K Mellinghoff; Fiscal Year: 2013
    ..This view has been challenged by the recent discovery that the majority of these tumors harbor an identical missense mutation in the catalytic pocket of the metabolic enzyme isocitrate dehydrogenase (IDH)...
  17. Excitability mechanisms of neurocardiac regulation
    ALBERT E GLASSCOCK; Fiscal Year: 2013
    ..model, which exhibits cardiac defects despite minimal cardiac expression;and 2) a Kcnq1 potassium channel missense mutation mouse model, which exhibits cardiac defects associated with co-expression in brain and heart...
  18. Role of PNPLA3 in Fatty Liver Disease
    HELEN HASKELL HOBBS; Fiscal Year: 2013
    ..Recently, we identified a missense mutation (I148M) in patatin-like phospholipase domain-containing protein, PNPLA3 that is strongly associated with ..
  19. Regulation of store-operated Ca2+ entry: STIM and ORAI
    Anjana Rao; Fiscal Year: 2013
    ..that Drosophila Stim and human STIM1 are key regulators of store-operated Ca2+ entry;and (iii) showed that a missense mutation in ORAI1 was responsible for a hereditary severe combined immundeficiency syndrome affecting two human ..
  20. FUNCTIONAL ANALYSES OF NEUROGLIAN/L1 IN SYNAPTOGENESIS
    TANJA ANGELA GODENSCHWEGE; Fiscal Year: 2012
    ..We found that a single missense mutation in the extracellular domain of the nrg849 allele disrupts the assembly and functionality of a central ..
  21. Molecular Mechanisms of the Hypoxic Response
    Frank S Lee; Fiscal Year: 2013
    ..we have identified a family with hereditary erythrocytosis (increased red blood cell mass) due to a G537W missense mutation in the HIF2A gene, and another family with erythrocytosis due to a P317R missense mutation in the PHD2 gene...
  22. CLONING GENES INVOLVED IN HEARING
    CYNTHIA CASSON MORTON; Fiscal Year: 2012
    ..DFNA9, using various experimental systems including investigation of a knock-in mouse model for a COCH missense mutation observed in DFNA9 by expression and proteomic analyses, (2) to continue to investigate human cochlear and ..
  23. Cell-specific RNA Targets of the Fragile X Mental Retardation Protein Family
    Jennifer C Darnell; Fiscal Year: 2013
    ..A missense mutation occurring in a Fragile X patient within an RNA binding domain of FMRP is sufficient to cause the disease and ..
  24. A Mouse Model for Glomerulosclerosis and Early Onset Renal Failure
    Vicki Huff; Fiscal Year: 2010
    ..To elucidate these mechanisms, we generated a novel mouse strain carrying a missense mutation (R394W) in the Wt1 gene which encodes a zinc finger transcription factor and is expressed in the glomerular ..
  25. Nuclear modifier genes for maternally inherited deafness
    Min Xin Guan; Fiscal Year: 2010
    ..Sequencing of TRMT1 in 392 members of an Arab-Israeli family and other Spanish/Italian families revealed a missense mutation (G28T) altering an invariant amino-acid residue (A10S) in the mitochondrial targeting sequence...
  26. The Role of Sema3D in Cardiac Development
    Karl Degenhardt; Fiscal Year: 2013
    ..A Sema3D missense mutation has been found in a patient with TAPVR...
  27. Intrathecal cyclodextrin therapy of feline Niemann-Pick type C disease
    Charles H Vite; Fiscal Year: 2013
    ..the pharmacologic, mechanistic, and toxicity issues in the feline model which has a spontaneously-occurring missense mutation in NPC1 (2864G-C) orthologous to the most common mutation in the most common form of NPC disease in patients ..
  28. Characterization of an FAD pathogenic PS1 mutation with complete loss of activity
    HANNAH LOUISE BRAUTIGAM; Fiscal Year: 2013
    ..2003) described the pathology and the genetics of the Tas-1 family;the pathogenic mutation in Tas-1 is a missense mutation, L271V, which disrupts alternative splicing of the PS1 gene, and results in a gene that lacks exon 8 (PS1 8)...
  29. Novel Mechanisms of Beta-lactam Resistance in Staph Aureus
    Binh An Diep; Fiscal Year: 2012
    ..Besides pbp4 and gdpP, a missense mutation was identified in arcB of the resistant mutant. Its contribution to resistance is not known...
  30. Photoperiod affects retinal function
    Chad R Jackson; Fiscal Year: 2012
    ..a link between alterations in retinal function and SAD, especially since previous research has shown that a missense mutation in the melanopsin gene could predispose humans to SAD (Roecklein, K.A., et al., 2009)...
  31. The Genetics and Cell Biology of the Epileptic Mouse Mutant Fitful
    Rebecca M Boumil; Fiscal Year: 2013
    ..Fitful is a missense mutation in an exon that defines the Dnm1a isoform, leaving intact the alternatively spliced exon that encodes Dnm1b...
  32. Mechanisms and regulation of post-translational modifications of Id proteins
    Antonio Iavarone; Fiscal Year: 2012
    ..Recently, we discovered that colon cancer cells acquire a missense mutation in the Id2 gene that converts Threonine-27 into the unphosphorylatable amino acid Alanine...
  33. MISMATCH REPAIR AND CARCINOGENESIS
    Richard Fishel; Fiscal Year: 2013
    ..We will apply our results to determine the functional defects associated with missense mutation found in LS/HNPCC families...
  34. Identifying a Hypoxia Inducible Factor target profile in Renal Cell Carcinoma tum
    Alexandra Arreola; Fiscal Year: 2013
    ..Tumor formation occurs when the normal copy of VHL is lost or inactivated. Given that VHL 2B missense mutation confers a high risk for RCC, the proposed project aims to identify key molecular changes that occur in renal ..
  35. Molecular Mechanisms Regulating Axon Guidance Receptor Activity
    William G Wadsworth; Fiscal Year: 2013
    ..We also uncovered a missense mutation within the unc-40 ectodomain sequence that in combination with unc-6(rh46) causes new axons migration ..
  36. Understanding the Pathogenic Mechanisms of Rett Syndrome
    Zhaolan Zhou; Fiscal Year: 2013
    ..of RTT, we previously developed and characterized a mouse model recapitulating an RTT-associated missense mutation, MeCP2 T158A...
  37. Regulation of Mutant P53 Expression and Oncogenic Activity
    Xinbin Chen; Fiscal Year: 2013
    ..The majority of tumor- derived p53 mutations is missense mutation and clustered within the central DNA-binding domain...
  38. The Sixth International Mdm2 Workshop
    James J Manfredi; Fiscal Year: 2011
    ..Indeed, a majority of human tumors have sustained missense mutation in the TP53 gene...
  39. The Role of Ribosome Biogenesis Factors in Liver Cirrhosis
    EMILY FRANCES FREED; Fiscal Year: 2012
    ..Recently, a missense mutation in the ribosome biogenesis protein, Cirhin, was reported to cause North American Indian childhood cirrhosis (..
  40. The Seventh International Mdm2 Workshop
    James J Manfredi; Fiscal Year: 2013
    ..Indeed, a majority of human tumors have sustained missense mutation in the TP53 gene...
  41. Pyrophosphorolysis-activatable helicase dependent amplification assay for lung ca
    BERTRAND LEMIEUX; Fiscal Year: 2007
    ..In Phase I we propose to focus on developing assays targeting a missense mutation in EGFR, L858R, is the second most common EGFR mutation...
  42. MOTOR FUNCTION OF CARDIAC B MYOSIN MUTANTS
    Mitsuo Ikebe; Fiscal Year: 1999
    ..of motor activity of human cardiac beta-myosin by in vitro motility assay: Identification of the effects of missense mutation on motor function; (4) Kinetic analysis of human cardiac beta-myosin ATPase cycle: Identification of effects ..
  43. Molecular Mechanisms of Ventricular Fibrillation
    JOSE JALIFE; Fiscal Year: 2007
    ..advantage of a unique knock-in mouse model (RyR2+/RyR2R4496C) that carries the murine equivalent of a human missense mutation (R4497C) in RyR2 that results in CPVT...
  44. Study of Ferroportin 1 in mammalian iron homeostasis
    Adriana Donovan; Fiscal Year: 2006
    ..In addition, we have identified a missense mutation in Fpn1 that is associated with the iron overload disorder autosomaldominant hemochromatosis...
  45. Hepatitis B virus e antigen expression
    Shuping Tong; Fiscal Year: 2004
    ..A Val to Phe missense mutation at residue 17 is frequently detected in HBV genomes isolated from seroconverted patients...
  46. Understanding the Role of COMT Variants in Sensorimotor Gating
    Victoria Risbrough; Fiscal Year: 2009
    A single nucleotide polymorphism (SNP), causing a missense mutation of codon 158 Valine to Methionine in the coding region (termed val158met), exists in the human catechol-o-methyltransferase (COMT) gene...
  47. The Role of Alpha Hemoglobin Stabilizing Protein in Human Beta Thalassemia
    Mitchell J Weiss; Fiscal Year: 2010
    ..Preliminary data support both mechanisms. First, we discovered a naturally occurring missense mutation, AHSP N75I, which impairs protein function and is associated with unexpectedly severe beta thalassemia in ..
  48. MOLECULAR GENETICS OF CONGENITAL ADRENAL HYPERPLASIA
    Perrin White; Fiscal Year: 2001
    ..The functional effects of each missense mutation will be determined by site-directed mutagenesis of cDNA and expression in cultured cells...
  49. Antioxidant Therapy for Ataxia Telangiectasia
    ROBERT SCHIESTL; Fiscal Year: 2009
    ..We have also shown that ATMASRI missense mutation homozygous as well as heterozygous mice show elevated frequencies of DNA deletions...
  50. 'IMMATURE SECRETION' VARIANTS OF HUMAN HEPATITIS B VIRUS
    Chiaho Shih; Fiscal Year: 2004
    ..The most frequent missense mutation found in the HBV core antigen occurs at codon 97 in chronic carriers worldwide (in 83 percent hepatoma ..
  51. INHIBITOR FORMATION IN GENE THERAPY FOR HEMOPHILIA
    Katherine High; Fiscal Year: 2001
    ..In dogs with hemophilia B resulting from a missense mutation in the F...
  52. Replication Control in Fragile X Syndrome
    BARBARA BOGGS; Fiscal Year: 2004
    ..examine replication timing in additional cell lines from patients with non-expansion mutations, including a missense mutation that affects one of the primary RNA binding domains and microdeletions affecting gene expression...
  53. The Role of Apoptosis in CryABR120G Heart Failure
    James Pattison; Fiscal Year: 2009
    ..CryAB is a small heat shock protein, which functions as a molecular chaperone. An Arg120Gly missense mutation in CryAB (CryABR120G) causes desmin related myopathy...
  54. IRON STATUS AND RISK OF CHD AND COLON CANCER
    Jing Ma; Fiscal Year: 2002
    ..capacity, ferritin) and genetic marker of hemochromatosis, an inherited disease of iron overload (C282Y, a missense mutation in HLA-H gene)...
  55. Improved Diagnosis and Treatment of Pearson's Syndrome
    Carol Saunders; Fiscal Year: 2001
    ..will involve the following specific aims: Aim 1: Establish the clinical relevance of a unique mitochondrial missense mutation affecting cytochrome b in a non-deletion case of PS...
  56. laminopathy Treatment with Farnesyltransferase Inhibitor
    Peter Gin; Fiscal Year: 2007
    ..Finally, I will test the possibility that FTIs might delay or prevent disease phenotypes in gene- targeted mice harboring a missense mutation (H222P) causing Emery-Dreifuss muscular dystrophy. [unreadable] [unreadable] [unreadable]
  57. METABOLIC CONSEQUENCES OF A PROHORMONE PROCESSING DEFECT
    JUERGEN NAGGERT; Fiscal Year: 2002
    ..A point mutation in the CPE gene causing a single missense mutation in the CPE molecule has been identified as the fat mutation...
  58. Signaling Pathways in Cardiac Hypertrophy
    STEPHEN LUCKEY; Fiscal Year: 2005
    ..include a mutation in the actin-binding domain of the murin alpha-myosin heavy chain (alpha-MHC), and both a missense mutation and a truncated molecule of cardiac troponin T (cTnT)...
  59. SYNUCLEINS--CELL BIOLOGY AND TRANSGENIC MICE
    Michael Lee; Fiscal Year: 1999
    ..PD are not known, genetic studies of familial PD (<10% of total cases of PD) have recently identified a missense mutation (A53T) in alpha-Synuclein (alpha-Syn)...
  60. ATM mutations in breast cancer - a functional approach
    Patrick Concannon; Fiscal Year: 2007
    ..abstract_text> ..
  61. Proteome analysis in mice expressing P301L tau
    Irving Vega; Fiscal Year: 2005
    ..of tauopathy in the FTDP-17 mouse model JNPL3, which expresses the human 4RON tau isoform bearing the P301L missense mutation. Previous studies demonstrated that in FTDP-17 P301L tau proteins undergo age- and pathological-dependent ..
  62. Missense mutant Atm and radiation-induced tumorgenesis
    Martin Lavin; Fiscal Year: 2005
    The overall aim of the project is to determine whether a missense mutation in the ATM gene (mutated in ataxia telengiectasia) predisposes heterozygous carriers to cancer and to investigate the mechanism of predisposition...
  63. Role of growth hormone in breast cancer
    Steven Swanson; Fiscal Year: 2006
    ..We have discovered that the Spontaneous Dwarf rat (SDR), which lacks GH due to a missense mutation in its GH gene, is nearly refractory to mammary cancer...