microcephaly

Summary

Summary: Abnormal smallness of the head, usually associated with mental retardation. (Dorland, 27th ed)

Top Publications

  1. pmc Cerebral organoids model human brain development and microcephaly
    Madeline A Lancaster
    Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna 1030, Austria
    Nature 501:373-9. 2013
  2. pmc Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors
    Sofia B Lizarraga
    Division of Genetics and the Manton Center for Orphan Disease Research, Children s Hospital Boston, Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Development 137:1907-17. 2010
  3. pmc CEP152 is a genome maintenance protein disrupted in Seckel syndrome
    Ersan Kalay
    Department of Medical Biology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
    Nat Genet 43:23-6. 2011
  4. pmc A primary microcephaly protein complex forms a ring around parental centrioles
    Joo Hee Sir
    Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK
    Nat Genet 43:1147-53. 2011
  5. ncbi Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome
    Louise S Bicknell
    Medical Research Council MRC Human Genetics Unit HGU, Institute for Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK
    Nat Genet 43:350-5. 2011
  6. pmc Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture
    Timothy W Yu
    Division of Genetics, Department of Medicine, Children s Hospital Boston, Boston, Massachusetts, USA
    Nat Genet 42:1015-20. 2010
  7. pmc Centrosomes and cilia in human disease
    Monica Bettencourt-Dias
    Instituto Gulbenkian de Ciencia, Oeiras, Portugal
    Trends Genet 27:307-15. 2011
  8. pmc Primary microcephaly: do all roads lead to Rome?
    Gemma K Thornton
    Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome MRC Building, Addenbrookes Hospital, Cambridge, UK
    Trends Genet 25:501-10. 2009
  9. pmc Cdk5rap2 exposes the centrosomal root of microcephaly syndromes
    Timothy L Megraw
    Department of Biomedical Sciences, Florida State University, College of Medicine, Tallahassee, USA
    Trends Cell Biol 21:470-80. 2011
  10. pmc The human microcephaly protein STIL interacts with CPAP and is required for procentriole formation
    Chieh Ju C Tang
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
    EMBO J 30:4790-804. 2011

Detail Information

Publications295 found, 100 shown here

  1. pmc Cerebral organoids model human brain development and microcephaly
    Madeline A Lancaster
    Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna 1030, Austria
    Nature 501:373-9. 2013
    ..Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice...
  2. pmc Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors
    Sofia B Lizarraga
    Division of Genetics and the Manton Center for Orphan Disease Research, Children s Hospital Boston, Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Development 137:1907-17. 2010
    b>Microcephaly affects approximately 1% of the population and is associated with mental retardation, motor defects and, in some cases, seizures...
  3. pmc CEP152 is a genome maintenance protein disrupted in Seckel syndrome
    Ersan Kalay
    Department of Medical Biology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
    Nat Genet 43:23-6. 2011
    ....
  4. pmc A primary microcephaly protein complex forms a ring around parental centrioles
    Joo Hee Sir
    Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK
    Nat Genet 43:1147-53. 2011
    Autosomal recessive primary microcephaly (MCPH) is characterized by a substantial reduction in prenatal human brain growth without alteration of the cerebral architecture and is caused by biallelic mutations in genes coding for a subset ..
  5. ncbi Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome
    Louise S Bicknell
    Medical Research Council MRC Human Genetics Unit HGU, Institute for Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK
    Nat Genet 43:350-5. 2011
    ..These findings establish a novel mechanism for the pathogenesis of microcephalic dwarfism and show a surprising but important developmental impact of impaired origin licensing...
  6. pmc Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture
    Timothy W Yu
    Division of Genetics, Department of Medicine, Children s Hospital Boston, Boston, Massachusetts, USA
    Nat Genet 42:1015-20. 2010
    Genes associated with human microcephaly, a condition characterized by a small brain, include critical regulators of proliferation, cell fate and DNA repair...
  7. pmc Centrosomes and cilia in human disease
    Monica Bettencourt-Dias
    Instituto Gulbenkian de Ciencia, Oeiras, Portugal
    Trends Genet 27:307-15. 2011
    ..Here, we give an overview of recent developments in this field, focusing on cancer, diseases of brain development and ciliopathies...
  8. pmc Primary microcephaly: do all roads lead to Rome?
    Gemma K Thornton
    Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome MRC Building, Addenbrookes Hospital, Cambridge, UK
    Trends Genet 25:501-10. 2009
    ..One approach for investigating neurogenesis is the study of autosomal recessive primary microcephaly (MCPH), in which prenatal brain growth is significantly reduced without an effect on brain structure...
  9. pmc Cdk5rap2 exposes the centrosomal root of microcephaly syndromes
    Timothy L Megraw
    Department of Biomedical Sciences, Florida State University, College of Medicine, Tallahassee, USA
    Trends Cell Biol 21:470-80. 2011
    Autosomal recessive primary microcephaly (MCPH) is characterized by small brain size as a result of deficient neuron production in the developing cerebral cortex...
  10. pmc The human microcephaly protein STIL interacts with CPAP and is required for procentriole formation
    Chieh Ju C Tang
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
    EMBO J 30:4790-804. 2011
    ..Mutations in STIL and CPAP/CENPJ cause primary microcephaly (MCPH)...
  11. pmc Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly
    Arun Kumar
    Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India
    Am J Hum Genet 84:286-90. 2009
    Primary microcephaly (MCPH) is an autosomal-recessive congenital disorder characterized by smaller-than-normal brain size and mental retardation. MCPH is genetically heterogeneous with six known loci: MCPH1-MCPH6...
  12. pmc Mutations in PNKP cause microcephaly, seizures and defects in DNA repair
    Jun Shen
    1 Howard Hughes Medical Institute, Department of Neurology, Beth Israel Deaconess Medical Center and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA 2 These authors contributed equally to the work
    Nat Genet 42:245-9. 2010
    ..We describe a previously unknown autosomal recessive disease characterized by microcephaly, early-onset, intractable seizures and developmental delay (denoted MCSZ)...
  13. pmc WD40-repeat protein 62 is a JNK-phosphorylated spindle pole protein required for spindle maintenance and timely mitotic progression
    Marie A Bogoyevitch
    Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia
    J Cell Sci 125:5096-109. 2012
    ..protein 62 (WDR62) was recently identified as a spindle pole protein linked to the neurodevelopmental defect of microcephaly but its roles in mitosis have not been defined...
  14. pmc Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4
    Duane L Guernsey
    Department of Pathology, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada
    Am J Hum Genet 87:40-51. 2010
    Primary microcephaly is a rare condition in which brain size is substantially diminished without other syndromic abnormalities...
  15. pmc A truncating mutation of CEP135 causes primary microcephaly and disturbed centrosomal function
    Muhammad Sajid Hussain
    Cologne Center for Genomics, University of Cologne, Cologne, Germany
    Am J Hum Genet 90:871-8. 2012
    Autosomal-recessive primary microcephaly (MCPH) is a rare congenital disorder characterized by intellectual disability, reduced brain and head size, but usually without defects in cerebral cortical architecture, and other syndromic ..
  16. pmc Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling
    Elen Griffith
    Medical Research Council MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
    Nat Genet 40:232-6. 2008
    ..These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental ..
  17. pmc Identification of microcephalin, a protein implicated in determining the size of the human brain
    Andrew P Jackson
    Molecular Medicine Unit, University of Leeds, United Kingdom
    Am J Hum Genet 71:136-42. 2002
    Primary microcephaly (MIM 251200) is an autosomal recessive neurodevelopmental condition in which there is a global reduction in cerebral cortex volume, to a size comparable with that of early hominids...
  18. pmc Human mutations in NDE1 cause extreme microcephaly with lissencephaly [corrected]
    Fowzan S Alkuraya
    Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
    Am J Hum Genet 88:536-47. 2011
    Genes disrupted in human microcephaly (meaning "small brain") define key regulators of neural progenitor proliferation and cell-fate specification...
  19. ncbi A patient with mutations in DNA Ligase IV: clinical features and overlap with Nijmegen breakage syndrome
    Tawfeg I Ben-Omran
    Division of Clinical and Metabolic Genetics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    Am J Med Genet A 137:283-7. 2005
    ..mutations in the LIG4 gene, closely resembles that of Nijmegen breakage syndrome (NBS), and is characterized by microcephaly, characteristic facial features, growth retardation, developmental delay, and immunodeficiency...
  20. ncbi A severe form of human combined immunodeficiency due to mutations in DNA ligase IV
    Anselm Enders
    Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany
    J Immunol 176:5060-8. 2006
    ..Impaired generation of immune diversity under conditions of limited LigIV activity can cause a human SCID variant with a characteristic immunological phenotype...
  21. ncbi The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis
    Fanny Kortüm
    Institut fur Humangenetik, Universitatsklinikum Hamburg Eppendorf, Campus Forschung, Martinistrase 52, 20246 Hamburg, Germany
    J Med Genet 48:396-406. 2011
    ..This study aimed to further characterise and delineate the phenotype of FOXG1 mutation positive patients...
  22. ncbi Spindle positioning in human cells relies on proper centriole formation and on the microcephaly proteins CPAP and STIL
    Daiju Kitagawa
    Swiss Institute for Experimental Cancer Research ISREC, School of Life Sciences, Swiss Federal Institute of Technology EPFL, Lausanne, Switzerland
    J Cell Sci 124:3884-93. 2011
    Patients with MCPH (autosomal recessive primary microcephaly) exhibit impaired brain development, presumably due to the compromised function of neuronal progenitors...
  23. ncbi Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum
    Juliane Najm
    Institut fur Humangenetik, Universitatsklinikum Hamburg Eppendorf, 20246 Hamburg, Germany
    Nat Genet 40:1065-7. 2008
    ..All five affected individuals with CASK mutations had congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia, and severe mental retardation.
  24. pmc Sex-dependent association of common variants of microcephaly genes with brain structure
    Lars M Rimol
    Division of Psychiatry, Oslo University Hospital Ulleval, 0407 Oslo, Norway
    Proc Natl Acad Sci U S A 107:384-8. 2010
    Loss-of-function mutations in the genes associated with primary microcephaly (MCPH) reduce human brain size by about two-thirds, without producing gross abnormalities in brain organization or physiology and leaving other organs largely ..
  25. ncbi Adaptive evolution of four microcephaly genes and the evolution of brain size in anthropoid primates
    Stephen H Montgomery
    Department of Zoology, University of Cambridge, Cambridge, United Kingdom
    Mol Biol Evol 28:625-38. 2011
    ..Genes linked to human primary microcephaly have received much attention as they have accelerated evolutionary rates along lineages leading to humans...
  26. pmc CtIP Mutations Cause Seckel and Jawad Syndromes
    Per Qvist
    Department of Human Genetics and Department of Biomedicine, Aarhus University, Aarhus, Denmark
    PLoS Genet 7:e1002310. 2011
    Seckel syndrome is a recessively inherited dwarfism disorder characterized by microcephaly and a unique head profile...
  27. pmc Identification of the DNA repair defects in a case of Dubowitz syndrome
    Jingyin Yue
    The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America
    PLoS ONE 8:e54389. 2013
    Dubowitz Syndrome is an autosomal recessive disorder with a unique set of clinical features including microcephaly and susceptibility to tumor formation...
  28. pmc Constitutional mutations in RTEL1 cause severe dyskeratosis congenita
    Amanda J Walne
    Centre for Paediatrics, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Barts and The London Children s Hospital, London, UK
    Am J Hum Genet 92:448-53. 2013
    ..They also demonstrate the severe multisystem consequences of its dysfunction...
  29. pmc Mutations in the β-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities
    Martin Breuss
    Institute of Molecular Pathology, Dr Bohr Gasse, Vienna 1030, Austria
    Cell Rep 2:1554-62. 2012
    ..Our results provide insight into the functional repertoire of the tubulin gene family, specifically implicating TUBB5 in embryonic neurogenesis and microcephaly.
  30. pmc Nijmegen breakage syndrome (NBS) with neurological abnormalities and without chromosomal instability
    E Seemanova
    Department of Clinical Genetics, Institute of Biology and Medical Genetics, 2nd Medical School of Charles University, Prague, Czech Republic
    J Med Genet 43:218-24. 2006
    ..The clinical phenotype is characterised by congenital microcephaly, mild dysmorphic facial appearance, growth retardation, immunodeficiency, and greatly increased risk for ..
  31. pmc A novel nonsense CDK5RAP2 mutation in a Somali child with primary microcephaly and sensorineural hearing loss
    Alistair T Pagnamenta
    NIHR Biomedical Research Centre, Oxford and Wellcome Trust Centre for Human Genetics, University of Oxford, UK
    Am J Med Genet A 158:2577-82. 2012
    Primary microcephaly is a genetically heterogeneous condition characterized by reduced head circumference (-3 SDS or more) and mild-to-moderate learning disability...
  32. ncbi Novel NDE1 homozygous mutation resulting in microhydranencephaly and not microlyssencephaly
    Ayse Guven
    Department of Molecular Biology and Genetics, Bogazici University, KP 301, Bebek, 34342 Istanbul, Turkey
    Neurogenetics 13:189-94. 2012
    ..Recently homozygous NDE1 mutations were reported in three kindred afflicted with extreme microcephaly with lissencephaly or microlissencephaly...
  33. pmc Mutations in WDR62 gene in Pakistani families with autosomal recessive primary microcephaly
    Rizwana Kousar
    Department of Biochemistry, Faculty of Biological Sciences, Quaid i Azam University, Islamabad, Pakistan
    BMC Neurol 11:119. 2011
    Autosomal recessive primary microcephaly is a disorder of neurogenic mitosis that causes reduction in brain size. It is a rare heterogeneous condition with seven causative genes reported to date...
  34. pmc Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities
    Nicola Brunetti-Pierri
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
    Nat Genet 40:1466-71. 2008
    ..Consistent and statistically significant features of microcephaly and macrocephaly were found in individuals with microdeletion and microduplication, respectively...
  35. pmc Haploinsufficiency of a spliceosomal GTPase encoded by EFTUD2 causes mandibulofacial dysostosis with microcephaly
    Matthew A Lines
    Children s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ontario, Canada
    Am J Hum Genet 90:369-77. 2012
    Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance...
  36. pmc Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy
    Pia Ostergaard
    Medical Genetics Unit, Biomedical Sciences, St George s University of London, UK
    Am J Hum Genet 90:356-62. 2012
    We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy...
  37. pmc Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation
    Yawei J Yang
    Division of Genetics and Manton Center for Orphan Disease Research, Boston Children s Hospital, Boston, MA 02115, USA
    Cell 151:1097-112. 2012
    b>Microcephaly is a neurodevelopmental disorder causing significantly reduced cerebral cortex size. Many known microcephaly gene products localize to centrosomes, regulating cell fate and proliferation...
  38. pmc Autosomal Recessive Primary Microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum
    Saqib Mahmood
    Department of Human Genetics and Molecular Biology, University of Health Sciences, Khayaban e Jamia Punjab, Lahore, 54600, Pakistan
    Orphanet J Rare Dis 6:39. 2011
    Autosomal Recessive Primary Microcephaly (MCPH) is a rare disorder of neurogenic mitosis characterized by reduced head circumference at birth with variable degree of mental retardation...
  39. ncbi The expanding phenotype of POMT1 mutations: from Walker-Warburg syndrome to congenital muscular dystrophy, microcephaly, and mental retardation
    Jeroen van Reeuwijk
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Hum Mutat 27:453-9. 2006
    ..unrelated families that result in a less severe phenotype than WWS, characterized by CMD with calf hypertrophy, microcephaly, and mental retardation...
  40. ncbi MRI evidence of white matter damage in a mouse model of Nijmegen breakage syndrome
    Yaniv Assaf
    Department of Neurobiochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
    Exp Neurol 209:181-91. 2008
    ..Conditional disruption of the murine ortholog of NBS1, Nbn, in the CNS of mice was previously reported to cause microcephaly, severe cerebellar atrophy and ataxia...
  41. pmc Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size
    Marwan Shinawi
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, Texas 77030, USA
    J Med Genet 47:332-41. 2010
    ..Deletion and the reciprocal duplication in 16p11.2 were recently associated with autism and developmental delay...
  42. pmc Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly
    Rikke S Møller
    Wilhelm Johannsen Centre for Functional Genome Research, Institute of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark
    Am J Hum Genet 82:1165-70. 2008
    We have identified and characterized two unrelated patients with prenatal onset of microcephaly, intrauterine growth retardation, feeding problems, developmental delay, and febrile seizures/epilepsy who both carry a de novo balanced ..
  43. ncbi Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IV
    Dietke Buck
    INSERM, Hopital Necker Enfants Malades, U429, Unité Développement Normal et Pathologique du Système Immunitaire, Paris, France
    Eur J Immunol 36:224-35. 2006
    ..hypomorphic and have only been described in six patients, four exhibiting mild immunodeficiency associated with microcephaly and developmental delay, while two patient had leukemia...
  44. ncbi High-resolution array CGH defines critical regions and candidate genes for microcephaly, abnormalities of the corpus callosum, and seizure phenotypes in patients with microdeletions of 1q43q44
    Blake C Ballif
    Signature Genomic Laboratories, Spokane, WA 99207, USA
    Hum Genet 131:145-56. 2012
    ..disability (ID) with limited or no expressive speech, characteristic facial features, hand and foot anomalies, microcephaly (MIC), abnormalities (agenesis/hypogenesis) of the corpus callosum (ACC), and seizures (SZR)...
  45. ncbi Novel CENPJ mutation causes Seckel syndrome
    Mohammed S Al-Dosari
    Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, MBC 03, PO Box 3354, Riyadh 11211, Saudi Arabia
    J Med Genet 47:411-4. 2010
    ..CONCLUSION This report establishes for the first time that mutation of CENPJ can lead to Seckel syndrome and calls for further investigation of the role played by other microcephaly related genes in the pathogenesis of PD.
  46. ncbi A clinical and molecular genetic study of 112 Iranian families with primary microcephaly
    H Darvish
    Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Kodakyar Street, Daneshjo Ave, Tehran, Iran
    J Med Genet 47:823-8. 2010
    Primary microcephaly (MCPH) is a genetically heterogeneous disorder showing an autosomal recessive mode of inheritance...
  47. pmc Differential DNA damage signaling accounts for distinct neural apoptotic responses in ATLD and NBS
    Erin R P Shull
    Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Genes Dev 23:171-80. 2009
    ..Neuropathology is a hallmark of these diseases, whereby neurodegeneration occurs in A-T and ATLD while microcephaly characterizes NBS...
  48. ncbi Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families
    M Willems
    Department of Genetics, Universite Paris Descartes, INSERM U781, Necker Hospital, 149 rue de Sevres, 75015 Paris, France
    J Med Genet 47:797-802. 2010
    ..group characterised by intrauterine growth retardation, severe proportionate short stature, and pronounced microcephaly. MOPD II is distinct from SCKL by more severe growth retardation, radiological abnormalities, and absent or ..
  49. pmc SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome
    Gregor D Gilfillan
    Department of Medical Genetics, Ulleval University Hospital, NO 0407 Oslo, Norway
    Am J Hum Genet 82:1003-10. 2008
    ..and DNA sequencing in a family exhibiting an X-linked mental retardation (XLMR) syndrome, characterized by microcephaly, epilepsy, ataxia, and absent speech and resembling Angelman syndrome, identified a deletion in the SLC9A6 gene ..
  50. pmc Recurrent reciprocal deletions and duplications of 16p13.11: the deletion is a risk factor for MR/MCA while the duplication may be a rare benign variant
    F D Hannes
    Center for Human Genetics, Herestraat 49, 3000 Leuven, Belgium
    J Med Genet 46:223-32. 2009
    ..Genomic disorders are often caused by non-allelic homologous recombination between segmental duplications. Chromosome 16 is especially rich in a chromosome-specific low copy repeat, termed LCR16...
  51. pmc Mutations in microcephalin cause aberrant regulation of chromosome condensation
    Marc Trimborn
    Institute of Human Genetics, Charité Universitary Medicine Berlin, Campus Virchow, Humboldt University, Berlin, Germany
    Am J Hum Genet 75:261-6. 2004
    Microcephalin (MCPH1) is a gene mutated in primary microcephaly, an autosomal recessive neurodevelopmental disorder in which there is a marked reduction in brain size...
  52. pmc Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes
    Heather C Mefford
    University of Washington School of Medicine, Seattle 98195, USA
    N Engl J Med 359:1685-99. 2008
    ..Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients...
  53. ncbi A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size
    Jacquelyn Bond
    Molecular Medicine Unit, University of Leeds, St James s University Hospital, Beckett Street, Leeds LS9 7TF, UK
    Nat Genet 37:353-5. 2005
    Autosomal recessive primary microcephaly is a potential model in which to research genes involved in human brain growth. We show that two forms of the disorder result from homozygous mutations in the genes CDK5RAP2 and CENPJ...
  54. pmc Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings
    C Geoffrey Woods
    Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge, United Kingdom
    Am J Hum Genet 76:717-28. 2005
    Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder. It is characterized by two principal features, microcephaly present at birth and nonprogressive mental retardation...
  55. ncbi Human microcephaly
    C Geoffrey Woods
    Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St James s University Hospital, Leeds LS9 7TF, UK
    Curr Opin Neurobiol 14:112-7. 2004
    b>Microcephaly is defined as a reduction in head circumference and this clinical finding infers that an individual has a significant diminution in brain volume...
  56. pmc Mutations in mouse Aspm (abnormal spindle-like microcephaly associated) cause not only microcephaly but also major defects in the germline
    Jeremy N Pulvers
    Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
    Proc Natl Acad Sci U S A 107:16595-600. 2010
    Mutations in ASPM (abnormal spindle-like microcephaly associated) cause primary microcephaly in humans, a disorder characterized by a major reduction in brain size in the apparent absence of nonneurological anomalies...
  57. pmc CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation
    Arijit Mukhopadhyay
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, The Netherlands
    Hum Genet 128:281-91. 2010
    b>Microcephaly, mental retardation and congenital retinal folds along with other systemic features have previously been reported as a separate clinical entity...
  58. ncbi What's the hype about CDK5RAP2?
    Nadine Kraemer
    Department of Pediatric Neurology, Charite, Universitatsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
    Cell Mol Life Sci 68:1719-36. 2011
    ..in the last years following the discovery, in 2005, that recessive mutations cause primary autosomal recessive microcephaly. This disease is seen as an isolated developmental defect of the brain, particularly of the cerebral cortex, ..
  59. pmc "Mandibulofacial dysostosis with microcephaly" caused by EFTUD2 mutations: expanding the phenotype
    Daniela V Luquetti
    Department of Pediatrics, University of Washington, Seattle, WA, USA
    Am J Med Genet A 161:108-13. 2013
    ..identified in 12 individuals with a rare sporadic craniofacial condition termed Mandibulofacial dysostosis with microcephaly (MIM 610536)...
  60. ncbi Syndrome of microcephaly, mental retardation, and tracheoesophageal fistula associated with features of Rett syndrome
    A K Shetty
    Department of Pediatrics, Louisiana State University Medical Center and Children s Hospital, New Orleans, USA
    J Child Neurol 15:61-3. 2000
    We report a 12-year-old girl with features of the syndrome of microcephaly, mesobrachydactyly, and tracheoesophageal fistula, who also developed distinctive features of Rett syndrome including regression of milestones with repetitive ..
  61. ncbi Microcephaly genes and the evolution of sexual dimorphism in primate brain size
    S H Montgomery
    Department of Zoology, University of Cambridge, Cambridge, UK
    J Evol Biol 26:906-11. 2013
    b>Microcephaly genes are amongst the most intensively studied genes with candidate roles in brain evolution...
  62. pmc Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome
    Tomoo Ogi
    Nagasaki University Research Centre for Genomic Instability and Carcinogenesis, Nagasaki University, Sakamoto, Nagasaki, Japan
    PLoS Genet 8:e1002945. 2012
    ..Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) ..
  63. pmc The desmosterolosis phenotype: spasticity, microcephaly and micrognathia with agenesis of corpus callosum and loss of white matter
    Jenny Zolotushko
    The Morris Kahn Laboratory of Human Genetics at the National Institute of Biotechnology in the Negev, Ben Gurion University of the Negev, Beer Sheva, Israel
    Eur J Hum Genet 19:942-6. 2011
    ..four surviving affected individuals, all presenting with severe failure to thrive, psychomotor retardation, microcephaly, micrognathia and spasticity with variable degree of hand contractures...
  64. ncbi Human RTEL1 deficiency causes Hoyeraal-Hreidarsson syndrome with short telomeres and genome instability
    Tangui Le Guen
    Inserm U768, Paris, France
    Hum Mol Genet 22:3239-49. 2013
    ..Collectively, these results identify RTEL1 as a novel HHS-causing gene and highlight its role as a genomic caretaker in humans. ..
  65. pmc Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly
    Karine Poirier
    Institut Cochin, Universite Paris Descartes, Centre National de la Recherche Scientifique CNRS, UMR 8104, Paris, France
    Nat Genet 45:639-47. 2013
    ....
  66. pmc Deletion 16p13.11 uncovers NDE1 mutations on the non-deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption
    Alex R Paciorkowski
    Departments of Neurology, Pediatrics, and Biomedical Genetics, Center for Neural Development and Disease, University of Rochester Medical Center, Rochester, NY 14642, USA
    Am J Med Genet A 161:1523-30. 2013
    ..We report on two unrelated patients with severe microcephaly, agenesis of the corpus callosum, scalp rugae, and a fetal brain disruption (FBD)-like phenotype with inherited ..
  67. pmc Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability
    Andres Moreno-De-Luca
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
    J Med Genet 48:141-4. 2011
    ..Hypoxic-ischaemic injury, long considered the most frequent causative factor, accounts for fewer than 10% of cases, whereas a growing body of evidence suggests that diverse genetic abnormalities likely play a major role...
  68. ncbi Kinetochore KMN network gene CASC5 mutated in primary microcephaly
    Anne Genin
    Institute of Interdisciplinary Research IRIBHM, Universite Libre de Bruxelles, Anderlecht, Belgium
    Hum Mol Genet 21:5306-17. 2012
    ..genes expressed at the centrosome or spindle pole have been reported to underlie autosomal recessive primary microcephaly (MCPH), a neurodevelopmental disorder consisting of an important brain size reduction present since birth, ..
  69. ncbi Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations
    V Bhat
    Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India
    Clin Genet 80:532-40. 2011
    Primary microcephaly is an autosomal recessive disorder characterized by smaller than normal brain size and mental retardation. It is genetically heterogeneous with seven loci: MCPH1-MCPH7...
  70. pmc Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay
    Miao He
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
    J Clin Invest 121:976-84. 2011
    ..recessive syndrome in a human patient with psoriasiform dermatitis, arthralgias, congenital cataracts, microcephaly, and developmental delay...
  71. ncbi Craniofacial morphology, dentition, and skeletal maturity in four siblings with Seckel syndrome
    I Kjaer
    Department of Orthodontics, Faculty of Health Sciences, University of Copenhagen, Nørre Allé 20, DK 2000 Copenhagen, Denmark
    Cleft Palate Craniofac J 38:645-51. 2001
    ..To describe the craniofacial morphology, dentition, and hand maturity in four siblings with Seckel syndrome...
  72. pmc Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair
    John J Reynolds
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton, BN1 9RQ, UK
    Nucleic Acids Res 40:6608-19. 2012
    b>Microcephaly with early-onset, intractable seizures and developmental delay (MCSZ) is a hereditary disease caused by mutations in polynucleotide kinase/phosphatase (PNKP), a DNA strand break repair protein with DNA 5'-kinase and DNA 3'-..
  73. pmc PTCH1 duplication in a family with microcephaly and mild developmental delay
    Katarzyna Derwinska
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Eur J Hum Genet 17:267-71. 2009
    ..32 in a 21-month-old boy with developmental delay, failure to thrive, and microcephaly. The same duplication was identified in the patient's mother who is also microcephalic and mildly delayed...
  74. ncbi Osteosclerotic bone dysplasia in siblings with a Fam20C mutation
    Mélanie Fradin
    Service de Genetique Medicale, CHU Strasbourg, Hopital de Hautepierre, Avenue Moliere, Strasbourg, France
    Clin Genet 80:177-83. 2011
    ..This case report also prompted us to revisit the FAM20 gene classification and allowed us to highlight the ancestral status of Fam20C...
  75. ncbi Microcephaly and simplified gyral pattern of the brain associated with early onset insulin-dependent diabetes mellitus
    M C Y de Wit
    Department of Pediatric Neurology, Erasmus Medical Center Sophia Children s Hospital, Rotterdam, The Netherlands
    Neurogenetics 7:259-63. 2006
    Two families are presented with a child suffering from microcephaly with a simplified gyral pattern of the brain (SGP) and early onset insulin dependent diabetes mellitus (IDDM)...
  76. ncbi The role of the DNA damage response pathways in brain development and microcephaly: insight from human disorders
    Mark O'Driscoll
    Genome Damage and Stability Centre, University of Sussex, Brighton, East Sussex BN1 9RQ, UK
    DNA Repair (Amst) 7:1039-50. 2008
    ..b>Microcephaly, representing reduced brain size, is a feature common to a diverse range of DDR-defective disorders...
  77. pmc Primary autosomal recessive microcephaly (MCPH1) maps to chromosome 8p22-pter
    A P Jackson
    Molecular Medicine Unit, St James s University Hospital, Leeds LS9 7TF, United Kingdom
    Am J Hum Genet 63:541-6. 1998
    Primary (or "true") microcephaly is inherited as an autosomal recessive trait and is thought to be genetically heterogeneous...
  78. pmc Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors
    Cathryn J Poulton
    Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
    Am J Hum Genet 89:265-76. 2011
    We describe a syndrome of primary microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes in two unrelated consanguineous families with at least three ..
  79. pmc Angelman syndrome protein UBE3A interacts with primary microcephaly protein ASPM, localizes to centrosomes and regulates chromosome segregation
    Pooja Singhmar
    Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, Karnataka, India
    PLoS ONE 6:e20397. 2011
    Many proteins associated with the phenotype microcephaly have been localized to the centrosome or linked to it functionally. All the seven autosomal recessive primary microcephaly (MCPH) proteins localize at the centrosome...
  80. pmc Microcephalin and pericentrin regulate mitotic entry via centrosome-associated Chk1
    Alexandra Tibelius
    Clinical Cooperation Unit Molecular Hematology Oncology, German Cancer Research Center, 69120 Heidelberg, Germany
    J Cell Biol 185:1149-57. 2009
    Primary microcephaly, Seckel syndrome, and microcephalic osteodysplastic primordial dwarfism type II (MOPD II) are disorders exhibiting marked microcephaly, with small brain sizes reflecting reduced neuron production during fetal life...
  81. ncbi Two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly
    Yoshiyuki Matsumoto
    Department of Genetics and Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi 1 2 3, Hiroshima 734 8553, Japan
    DNA Repair (Amst) 10:314-21. 2011
    ..in the NBN gene underlie Nijmegen breakage syndrome (NBS), a chromosomal instability syndrome characterized by microcephaly, bird-like faces, growth and mental retardation, and cellular radiosensitivity...
  82. ncbi 2q23 de novo microdeletion involving the MBD5 gene in a patient with developmental delay, postnatal microcephaly and distinct facial features
    Brian H Y Chung
    Division of Clinical and Metabolic Genetics, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada
    Am J Med Genet A 155:424-9. 2011
    ..She had short stature, microcephaly, and distinct facial features. Her speech was dysarthric, and she demonstrated repetitive hand movements...
  83. ncbi Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis
    Lekbir Baala
    Departement de Genetique Medicale, Institut National D Hygiene, Rabat, Maroc
    Nat Genet 39:454-6. 2007
    ..We report an autosomal recessive microcephaly syndrome cosegregating with a homozygous balanced translocation between chromosomes 3p and 10q, and we show ..
  84. ncbi Microdeletion of 17q22q23.2 encompassing TBX2 and TBX4 in a patient with congenital microcephaly, thyroid duct cyst, sensorineural hearing loss, and pulmonary hypertension
    Manjunath Nimmakayalu
    Division of Medical Genetics, Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
    Am J Med Genet A 155:418-23. 2011
    ..Shared clinical features in this group of patients include microcephaly, prenatal onset growth restriction, heart defects, tracheoesophageal fistula, and esophageal atresia (TEF/EA), ..
  85. pmc A third novel locus for primary autosomal recessive microcephaly maps to chromosome 9q34
    L Moynihan
    Molecular Medicine Unit, St James s University Hospital, Leeds, United Kingdom
    Am J Hum Genet 66:724-7. 2000
    Primary autosomal recessive microcephaly is a clinical diagnosis of exclusion in an individual with a head circumference >/=4 SDs below the expected age-and-sex mean...
  86. ncbi A 6.9 Mb 1qter deletion/4.4 Mb 18pter duplication in a boy with extreme microcephaly with simplified gyral pattern, vermis hypoplasia and corpus callosum agenesis
    Joris Andrieux
    Eur J Med Genet 51:87-91. 2008
    ..4 Mb 18pter duplication. Numerous 1qter deletions have already been described associated with brain malformations. Among 1q44 deleted genes, AKT3 is the strongest candidate gene for vermis hypoplasia and corpus callosum agenesis...
  87. ncbi Evolution of primary microcephaly genes and the enlargement of primate brains
    Chris Ponting
    MRC Functional Genetics, University of Oxford, Department of Human Anatomy and Genetics, South Parks Road, Oxford OX1 3QX, UK
    Curr Opin Genet Dev 15:241-8. 2005
    ..Microcephalin (MCPH1) and Abnormal spindle-like microcephaly associated (ASPM) are genes mutated in primary microcephaly, a human neurodevelopmental disorder...
  88. ncbi A common SNP of MCPH1 is associated with cranial volume variation in Chinese population
    Jin kai Wang
    State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, PR China
    Hum Mol Genet 17:1329-35. 2008
    b>Microcephaly (MCPH) genes are informative in understanding the genetics and evolution of human brain volume...
  89. ncbi Periventricular heterotopia: phenotypic heterogeneity and correlation with Filamin A mutations
    E Parrini
    Research Institute, I R C C S, Stella Maris Foundation, University of Pisa, Italy
    Brain 129:1892-906. 2006
    ..A rare, recessive form of bilateral PNH with microcephaly and severe delay is associated with mutations of the ADP-ribosylation factor guanine nucleotide-exchange factor-..
  90. ncbi ASPM is a major determinant of cerebral cortical size
    Jacquelyn Bond
    Molecular Medicine Unit, University of Leeds, St James s University Hospital, Beckett Street, Leeds LS9 7TF, UK
    Nat Genet 32:316-20. 2002
    ..Humans with autosomal recessive primary microcephaly (MCPH) show a small but otherwise grossly normal cerebral cortex associated with mild to moderate mental ..
  91. ncbi Mutation analysis of the ASPM gene in 18 Pakistani families with autosomal recessive primary microcephaly
    Rizwana Kousar
    Department of Biochemistry, Faculty of Biological Sciences, Quaid i Azam University, Islamabad, Pakistan
    J Child Neurol 25:715-20. 2010
    Autosomal recessive primary microcephaly (MCPH) is a rare neurological disorder, in which the patients exhibit reduced occipital frontal head circumference (>3 standard deviations) and mild-to-severe mental retardation...
  92. pmc 3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis
    J Jaeken
    Department of Paediatrics, University Hospital Gasthuisberg, Leuven, Belgium
    Arch Dis Child 74:542-5. 1996
    Serine concentrations were markedly decreased in the cerebrospinal fluid of two brothers with congenital microcephaly, profound psychomotor retardation, hypertonia, epilepsy, growth retardation, and hypogonadism...
  93. pmc A truncating mutation of TRAPPC9 is associated with autosomal-recessive intellectual disability and postnatal microcephaly
    Ganeshwaran H Mochida
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Am J Hum Genet 85:897-902. 2009
    ..a genetic locus for autosomal-recessive nonsyndromic intellectual disability associated with variable postnatal microcephaly through homozygosity mapping of a consanguineous Israeli Arab family...
  94. ncbi Hypomyelination and reversible white matter attenuation in 3-phosphoglycerate dehydrogenase deficiency
    T J de Koning
    Department of Pediatric Metabolic Diseases, University Medical Centre Utrecht, The Netherlands
    Neuropediatrics 31:287-92. 2000
    ..They presented with congenital microcephaly, severe psychomotor retardation and intractable seizures...
  95. ncbi Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids
    T J de Koning
    Department of Metabolic Diseases, University Medical Center Utrecht, The Netherlands
    J Inherit Metab Dis 25:119-25. 2002
    Congenital microcephaly, intractable seizures and severe psychomotor retardation characterize 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, a disorder of L-serine biosynthesis...
  96. pmc Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure
    Bernd Gruhn
    Department of Pediatrics, University of Jena, Kochstr, 2, D 07740 Jena, Germany
    Orphanet J Rare Dis 2:5. 2007
    ..The clinical phenotype shows overlap with a number of other rare syndromes, including Seckel syndrome, Nijmegen breakage syndrome, and Fanconi anemia. Thus the clinical diagnosis is often delayed and established by exclusion...
  97. ncbi Genetic links between brain development and brain evolution
    Sandra L Gilbert
    Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Illinois 60637, USA
    Nat Rev Genet 6:581-90. 2005
    ..Recent studies have shown that genes controlling brain development - notably those implicated in microcephaly (a congenital defect that is characterized by severely reduced brain size) - are favoured targets of natural ..
  98. ncbi Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome
    R Varon
    Institute of Human Genetics, Charite Humboldt University, Berlin, Germany
    Cell 93:467-76. 1998
    Nijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition...
  99. ncbi A novel deletion mutation in CENPJ gene in a Pakistani family with autosomal recessive primary microcephaly
    Asma Gul
    Department of Biochemistry, Faculty of Biological Sciences, Quaid i Azam University, Islamabad, Pakistan
    J Hum Genet 51:760-4. 2006
    Autosomal recessive primary microcephaly (MCPH) is a rare human genetic disorder in which the head circumference is reduced because of abnormality in fetal brain growth...
  100. ncbi Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly
    Dietke Buck
    INSERM, Hopital Necker Enfants Malades, U768 Unité Développement Normal et Pathologique du Système Immunitaire, Paris, France
    Cell 124:287-99. 2006
    ..Here we describe five patients with growth retardation, microcephaly, and immunodeficiency characterized by a profound T+B lymphocytopenia...
  101. ncbi Many roads lead to primary autosomal recessive microcephaly
    Angela M Kaindl
    INSERM, U676, Paris, France
    Prog Neurobiol 90:363-83. 2010
    Autosomal recessive primary microcephaly (MCPH), historically referred to as Microcephalia vera, is a genetically and clinically heterogeneous disease...

Research Grants62

  1. Mechanisms of ethanol-induced neurodevelopmental effects
    Marina Guizzetti; Fiscal Year: 2011
    ..during brain development as a consequence of these genetic defects leads to severe brain damage, including microcephaly and mental retardation, both of which are hallmarks of the fetal alcohol syndrome...
  2. Evolution of the Immune Response to Cytomegalovirus Transmitted via Breast Milk
    Lynn Puddington; Fiscal Year: 2010
    ..For example, human cytomegalovirus (HCMV) infection in utero (congenital) can result in growth retardation, microcephaly, sensorineural hearing loss, and even death...
  3. Molecular and cellular mechanism of Microcephaly
    Arnold Kriegstein; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Autosomal recessive primary microcephaly (MCPH) is a genetically and clinically heterogeneous disease defined by a decrease in head circumference at birth...
  4. Centrosomin and Centrosomes in Cell Division
    Timothy L Megraw; Fiscal Year: 2012
    ..systems and achieve a closer understanding of the pathology that underlies mutations in CDK5RAP2, which cause microcephaly in humans. CNN contains two conserved modules...
  5. Genetic Analysis of Mouse Nervous System Development
    Kathryn V Anderson; Fiscal Year: 2013
    ..Cilia are templated by centrosomes, and human genetic diseases that disrupt the centrosome cause microcephaly. Aim 3 of the proposal will define the developmental and cellular functions of centrosomes in the early embryo ..
  6. Fundamental mechanisms of protein kinase activation loop autophosphorlyation
    Vaughn Cleghon; Fiscal Year: 2013
    ..The DYRK family of kinases for example, plays important roles in Down Syndrome, microcephaly, cancer, and Alzheimer's disease...
  7. Microcephaly in an RNAi mouse with reduced sulfation
    Nancy B Schwartz; Fiscal Year: 2010
    ..5. Mice from these matings survive to adulthood but have brains that are markedly smaller (microcephaly) than control littermates...
  8. Repair of HCMV-Induced DNA Damage in Infected Cells
    Elizabeth A Fortunato; Fiscal Year: 2013
    ..infection are primarily observed in the central nervous system (CNS) and include hearing loss, vision loss, microcephaly and mental retardation...
  9. ATM and DNA Damage in the Nervous System
    Peter J McKinnon; Fiscal Year: 2013
    ..result in a variety of human diseases, many of which impact the nervous system leading to neurodegeneration, microcephaly or brain tumors...
  10. Rapid and inexpensive screening of disease candidate genes in mice
    KATHLEEN JOYCE MILLEN; Fiscal Year: 2010
    ..mouse models of human structural birth defects of the cerebellum and cerebrum (Dandy-Walker malformation, microcephaly) and severe congenital heart defects (Holt-Oram Syndrome and Conotruncal malformations)...
  11. Pyruvate Dehydrogenase E1: Structure-Function Studies
    William F Furey; Fiscal Year: 2012
    ..beri-beri, maple syrup urine disease, Pyruvate Dehydrogenase Deficiency (PDHA) associated lactic acidosis, microcephaly, motor neuropathy, Leigh syndrome, and neurological diseases including Alzheimer's and Parkinson's...
  12. Training in Neurogenetics: Function of NUP107 in Human and Mouse
    Bethany N Sotak; Fiscal Year: 2012
    ..Autosomal recessive primary microcephaly (MCPH) is characterized by an abnormally a reduction of brain growth...
  13. CELL IDENTITY DETERMINATION IN CEREBRAL CORTEX
    Christopher A Walsh; Fiscal Year: 2013
    ..In the previous funding period of this grant we studied of the mechanisms of several causes of microcephaly (small cerebral cortex), these studies suggest that microcephaly genes play important roles in the control of ..
  14. Katanin p80: A Role for Regulation of Microtubule Severing in Cortical Developmen
    WEN FAN HU; Fiscal Year: 2013
    ..Mutations in genes causing microcephaly encode proteins that localize to the centrosome and pericentriolar matrix, suggesting that this is the seat of ..
  15. Regulation of Centrosome Assembly by Phosphorylation
    Mi Hye Song; Fiscal Year: 2012
    ..A mutation in the putative human homolog (SIL/STIL) of SAS-5 is linked to primary microcephaly (MCPH), an autosomal- recessive congenital disorder with reduced brain size...
  16. Neonatal Biomarkers in Extremely Preterm Babies Predict Childhood Brain Disorders
    Karl Kuban; Fiscal Year: 2013
    ..11% had cerebral palsy, 40% had a developmental quotient below 70, and 11% had microcephaly. Placenta organisms and histologic characteristics, as well as proteins measured in the blood of these infants ..
  17. Mechanisms Underlying Specification of Neuronal Projection Identity in the Cortex
    Karpagam Srinivasan; Fiscal Year: 2010
    ..A developmental abnormality in these circuits leads to several mental disorders, including microcephaly (Meckel-Grueber syndrome) and microlissencephaly, X-linked form of Kallmann syndrome...
  18. The Mechanism of Pericentriolar Material Assembly During Centrosome Biogenesis
    Tomer Avidor-Reiss; Fiscal Year: 2013
    ..of these developmental disorders are cystic kidney disease, Bardet-Biedl syndrome, left-right asymmetry, and Microcephaly. Clearly, proper centrosomes biogenesis is essential to human health...
  19. Molecular basis for ligation of mismatched DNA ends
    Gilbert Chu; Fiscal Year: 2012
    ..However, some of the mutations cause microcephaly and growth delay, while others cause severe combined immunodeficiency...
  20. Regulation and Function of ERK5 in CNS neurons
    Zhengui Xia; Fiscal Year: 2010
    ..Abnormalities in these processes have been implicated in microcephaly and in several forms of mental disorders including mental retardation, depression, and schizophrenia...
  21. Neurogenesis: Career Development Plan in the Genetic and Modeling of Microcephaly
    STEPHANIE LEE BIELAS; Fiscal Year: 2011
    ..to tailor this new technology to model defects in neurogenesis which underlie autosomal recessive primary microcephaly (MCPH)...
  22. DNA Breaks and Repair During Neuronal Development
    EDWARD CHARLES GILMORE; Fiscal Year: 2011
    ..We have identified a new genetic syndrome of mental retardation, severe microcephaly, disabling seizures and behavioral problems called microcephaly with seizures (MCSZ)...
  23. The Molecular roles of Filamin A and Arfgef2 in cortical development
    JASON B NEAL; Fiscal Year: 2010
    ..neuronal nodule formation along the lateral ventricles of the brain suggesting defects in neuronal migration 2) microcephaly, suggesting defects in neural proliferation 3) dyslexia, suggesting abberent cortical connectivity...
  24. Neurogenesis: Career Development Plan in the Genetic and Modeling of Microcephaly
    STEPHANIE LEE BIELAS; Fiscal Year: 2013
    ..to tailor this new technology to model defects in neurogenesis which underlie autosomal recessive primary microcephaly (MCPH)...
  25. Gng5 function in neural progenitors
    Janet D Robishaw; Fiscal Year: 2013
    ..Moreover, we have shown that global deletion of Gng5 causes microcephaly. However, the information that can be obtained from studying the global knockout mice has been limited by their ..
  26. Investigation of DUF1220 Domains in Human Brain Function and Disease
    James M Sikela; Fiscal Year: 2013
    ..g. autism, mental retardation, schizophrenia, microcephaly and macrocephly...
  27. Mechanism and regulation of V(D)J repair
    Patricia Cortes; Fiscal Year: 2013
    ..have not been described yet, but interestingly, Cernunnos/XLF mutations in humans result in growth defects, microcephaly and immunodeficiency, similar to what has been observed for Ligase IV mutations...
  28. Stem Cells of the Developing Human Neocortex
    Arnold Kriegstein; Fiscal Year: 2013
    ..that have genetic or developmental origins, ranging from cortical malformations such as lissencephaly and microcephaly to more subtle defects like epilepsy, autism, and schizophrenia...
  29. Roles of engrailed proteins in granule cells during cerebellum development
    RYAN TERRENCE WILLETT; Fiscal Year: 2013
    ..is particularly emphasized by the observation of changes in brain subregion size in numerous diseases, such as microcephaly, schizophrenia and autism spectrum disorder...
  30. Analysis of the Exon Junction Complex in Neural Development and Microcephaly
    DEBRA LYNN SILVER; Fiscal Year: 2013
    ..to this training is a panel of advisors that bring together expertise in mouse embryology, neural development, microcephaly, and mitosis...
  31. Mitotic functions of cilia proteins
    Stephen J Doxsey; Fiscal Year: 2013
    ..Centrosome anomalies affect the fidelity of spindle and cilia function and are associated with ciliopathies, microcephaly, dwarfism, cancer and other human disorders...
  32. ISOLATION OF NOVEL MUTATIONS AFFECTING THE MOUSE EMBRYO
    Kathryn V Anderson; Fiscal Year: 2013
    ..will define the genes and mechanisms that are responsible for congenital malformations such as situs inversus, microcephaly, and heart defects...
  33. Transgenic mice containing human DUF1220 domains
    James M Sikela; Fiscal Year: 2011
    ..1 associated with a number of cognitive diseases including autism, schizophrenia and microcephaly. Given the potential importance of DUF1220 to human cognitive disease and brain evolution, the goal of this ..
  34. Transgenic mice containing human DUF1220 domains
    James M Sikela; Fiscal Year: 2012
    ..1 associated with a number of cognitive diseases including autism, schizophrenia and microcephaly. Given the potential importance of DUF1220 to human cognitive disease and brain evolution, the goal of this ..
  35. PREVENTION OF X-RAY INDUCED MALFORMATIONS
    MARVIN SODICOFF; Fiscal Year: 1990
    ..Gross malformations of the CNS e.g., exencephaly or microcephaly and skeletal defects such as disorganization or absence of the ossification centers of the vertebrae, ribs, and ..
  36. Mechanisms of neural progenitor division in the developing brain
    DEBRA LYNN SILVER; Fiscal Year: 2013
    ..Our previous NIH-funded studies demonstrated that Magoh mutants exhibit microcephaly, with brains 30% smaller than normal, largely due to reduced neural progenitors...
  37. Double-Strand Break Repair and Genome Stability
    Paul Russell; Fiscal Year: 2013
    ..Notably, hypomorphic mutations in human Nbs1 cause microcephaly, developmental abnormalities, immunodeficiency, radiation sensitivity and cancer predisposition...
  38. Effects of Dioxin on Vietnamese Civilians
    David Carpenter; Fiscal Year: 2004
    ..will study cases of a) cleft lip/cleft palate, b) neural tube defects, including spina bifida, anecephaly and microcephaly, and c) limb abnormalities/limb reduction...
  39. COCAINE AND PERINATAL CEREBRAL AND UMBILICAL VESSELS
    Michael Schreiber; Fiscal Year: 1992
    ..Complications include intracranial hemorrhage, cerebral infarction, microcephaly, and seizures...
  40. Molecular Mechanisms of Primary Microcephaly
    Angeliki Louvi; Fiscal Year: 2013
    ..The objective of this application is to examine the molecular mechanisms underlying Autosomal Recessive Primary Microcephaly. It is based on the identification of homozygous mutations in WDR62 in individuals with primary microcephaly ..
  41. MOLECULAR MECHANISMS OF NEOCORTICAL NEUROGENESIS
    Joseph J LoTurco; Fiscal Year: 2012
    ..The specific role of these primary microcephaly (MCPH) genes in neural progenitors has yet to be fully defined...
  42. HBAA--A MARKER OF FETAL ALCOHOL EXPOSURE
    Lewis Holmes; Fiscal Year: 1993
    ..Growth retardation and microcephaly are the most common effects of prenatal exposure to an excessive amount of alcohol...
  43. MODELS OF MR/DD AND RISKS OF ABERRANT BEHAVIOR
    RICHARD TESSEL; Fiscal Year: 1999
    ..g., "irreversible" depletions of striatal dopamine and its metabolites) and microcephaly (M; e.g...
  44. Dietary Control of PKU with Glycomacropeptide from Whey
    Denise Ney; Fiscal Year: 2007
    ..This is a clear risk for pregnant women with PKU whose infants show microcephaly, decreased IQ and/or congenital heart disease when exposed to maternal phe levels > 6-10 mg/dL...
  45. Intravenous non-viral gene therapy for phenylketonuria (PKU)
    Cary Harding; Fiscal Year: 2006
    ..Contemporary dietary therapy for PKU, although preventing the major manifestations of the disease (seizures, microcephaly, mental retardation), requires life-long commitment to an unpalatable and expensive diet...
  46. Functional studies on normal neural aneuploidy
    Jerold Chun; Fiscal Year: 2007
    ..retardation, and multiple variegated aneuploidy (MVA) that shows a range of aneuploidies and is associated with microcephaly and mental retardation...
  47. Ethanol and cholesterol homeostasis in the brain
    Marina Guizzetti; Fiscal Year: 2006
    ..development as a consequence of these genetic defects leads, among others, to severe brain damage including microcephaly and mental retardation, both of which are hallmarks of fetal alcohol syndrome...
  48. SCREEN FOR LYMPHOID MUTANTS
    Nikolaus Trede; Fiscal Year: 2004
    ..One of these mutants, CZ-3, is an autosomal recessive mutation which results in microcephaly, microphthalmia and abnormalities of the pharyngeal arches...
  49. MOLECULAR MECHANISMS LEADING TO RETT SYNDROME
    Uta Francke; Fiscal Year: 2002
    ..onset that is characterized by developmental regression with loss of speech an of purposeful hand use, microcephaly and seizures...
  50. Genetic Analysis of Microcephaly in Tunisian Population
    Christopher Walsh; Fiscal Year: 2009
    b>Microcephaly refers to a condition in which the human brain fails to achieve normal size. It is associated with mental retardation, developmental delay, neuromotor disability, and epilepsy...
  51. COMPLEMENTATION OF THE NIJMEGEN BREAKAGE SYNDROME DEFECT
    CORDULA KIRCHGESSNER; Fiscal Year: 1999
    Nijmegen Breakage syndrome (NBS) is a rare inherited human disorder characterized by immune deficiencies, microcephaly, developmental delay and cancer susceptibility...
  52. MOLECULAR ANALYSIS OF ETHANOL-INDUCED OROFACIAL DEFECTS
    M Pisano; Fiscal Year: 1993
    ..alcohol syndrome" (FAS), include: 1) pre- and postnatal growth retardation, 2) cranial/facial defects such as microcephaly, short palpebral fissures, midfacial hypoplasia, and cleft lip and/or cleft palate and 3) central nervous ..
  53. ATM and DNA Damage in the Nervous System
    PETER MCKINNON; Fiscal Year: 2007
    ..characterized by DMA repair defects feature with neuropathology ranging from profound neurodegeneration to microcephaly to brain tumors...
  54. CONGENITAL MICROCEPHALY
    Alan Leviton; Fiscal Year: 1993
    ..This has led to the view that congenital microcephaly is an indicator of disturbed brain growth and development in utero...
  55. SOCIAL SUPPORT FOR FAMILIES OF HIGH RISK INFANTS
    CARL DUNST; Fiscal Year: 1991
    ..4) at-risk for retardation due to conditions known to lead to mental retardation (Down syndrome, microcephaly, hydrocephaly, etc...
  56. CRI DU CHAT SYNDROME: GENE IDENTIFICATION
    JOAN OVERHAUSER; Fiscal Year: 1999
    ..Patients with this syndrome present with microcephaly, a round face, hypertelorism, micrognathia, prominent nasal bridge, epicanthal folds, hypotonia, and severe ..
  57. Apoptosis in the ethanol exposed neonatal brain
    LORA WATTS; Fiscal Year: 2004
    ..There are a number of deficits which occur such as prenatal and postnatal deficiencies, microcephaly, and craniofacial abnormalities...
  58. Switching Kinetics in Calmodulin-IQ Domain Complexes
    Anthony Persechini; Fiscal Year: 2009
    ..and other mutations in the ASPM protein, which contains multiple IQ domain repeats, are associated with microcephaly, and the number of repeats appears to be positively correlated with brain size...
  59. Neurodevelopmental Outcome in Russian Orphanage
    Laurie Miller; Fiscal Year: 2004
    ..birth, including prenatal drug and alcohol exposure, prematurity, intrauterine growth retardation, congenital microcephaly, and lack of prenatal care...
  60. COCAINE & FETAL CEREBRAL BLOOD FLOW AND METABOLISM
    HISAYO MORISHIMA; Fiscal Year: 1993
    ..abnormalities and microcephaly in cocaine-exposed offspring...
  61. MATERNAL EPILEPSY: EFFECTS ON THE BRAIN AND OTHER ORGANS
    Lewis Holmes; Fiscal Year: 1993
    ..In the 01 to 03 years we have compared many outcomes; the frequency of one or more of five (microcephaly, growth retardation, major malformation, the "anticonvulsant face" and fingernail hypoplasia) was 35...
  62. MR Metabolic Brain Imaging of the Infant Brain
    Daniel Vigneron; Fiscal Year: 2003
    ..We will also add these techniques to MR exams of age-matched infants being examined for macrocephaly, microcephaly, suspected mild trauma, or febrile seizures...