David R Fitzpatrick

Summary

Affiliation: National Institute for Medical Research
Country: UK

Publications

  1. ncbi request reprint Transcriptome analysis of human autosomal trisomy
    David R Fitzpatrick
    MRC Human Genetics Unit, Edinburgh EH4 2XU, UK
    Hum Mol Genet 11:3249-56. 2002
  2. ncbi request reprint Transcriptional consequences of autosomal trisomy: primary gene dosage with complex downstream effects
    David R Fitzpatrick
    MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK
    Trends Genet 21:249-53. 2005
  3. ncbi request reprint Identification of SATB2 as the cleft palate gene on 2q32-q33
    David R Fitzpatrick
    Cell and Molecualr Genentics, MRC Human Genetics Unit, Western General Hospital, Edinburgh, EH4 2XU, UK
    Hum Mol Genet 12:2491-501. 2003
  4. pmc Monoallelic and biallelic mutations in MAB21L2 cause a spectrum of major eye malformations
    Joe Rainger
    Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, Edinburgh EH4 2XU, UK
    Am J Hum Genet 94:915-23. 2014
  5. ncbi request reprint Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome
    Kathleen A Williamson
    Medical Genetics Section, MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK
    Hum Mol Genet 15:1413-22. 2006
  6. pmc Heterozygous loss-of-function mutations in YAP1 cause both isolated and syndromic optic fissure closure defects
    Kathleen A Williamson
    Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
    Am J Hum Genet 94:295-302. 2014
  7. pmc Bilateral renal agenesis/hypoplasia/dysplasia (BRAHD): postmortem analysis of 45 cases with breakpoint mapping of two de novo translocations
    Louise Harewood
    MRC Human Genetics Unit, Institute of Genetic and Molecular Medicine, Edinburgh, United Kingdom
    PLoS ONE 5:e12375. 2010
  8. pmc Disruption of SATB2 or its long-range cis-regulation by SOX9 causes a syndromic form of Pierre Robin sequence
    Jacqueline K Rainger
    MRC Human Genetics Unit, MRC Institute of Genetic and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
    Hum Mol Genet 23:2569-79. 2014
  9. doi request reprint 'Crommelin-type' symmetrical tetramelic reduction deformity: a new case and breakpoint mapping of a reported case with de-novo t(2;12)(p25.1;q23.3)
    Louise Harewood
    MRC Human Genetics Unit, Institute of Genetic and Molecular Medicine, Western General Hospital, Edinburgh EH4 2XU, UK
    Clin Dysmorphol 19:5-13. 2010
  10. doi request reprint Enhancer-adoption as a mechanism of human developmental disease
    Laura A Lettice
    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh
    Hum Mutat 32:1492-9. 2011

Detail Information

Publications42

  1. ncbi request reprint Transcriptome analysis of human autosomal trisomy
    David R Fitzpatrick
    MRC Human Genetics Unit, Edinburgh EH4 2XU, UK
    Hum Mol Genet 11:3249-56. 2002
    ..It seems likely that the degree of this misregulation determines the severity of the phenotype in most aneuploidy...
  2. ncbi request reprint Transcriptional consequences of autosomal trisomy: primary gene dosage with complex downstream effects
    David R Fitzpatrick
    MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK
    Trends Genet 21:249-53. 2005
    ..In this article, I propose a model of the main genetic mechanisms that are responsible for producing the transcriptional derangement associated with trisomy. This has implications for future study design...
  3. ncbi request reprint Identification of SATB2 as the cleft palate gene on 2q32-q33
    David R Fitzpatrick
    Cell and Molecualr Genentics, MRC Human Genetics Unit, Western General Hospital, Edinburgh, EH4 2XU, UK
    Hum Mol Genet 12:2491-501. 2003
    ..Despite the strong evidence supporting an important role for SATB2 in palate development, mutation analysis of 70 unrelated patients with CPO did not reveal any coding region variants...
  4. pmc Monoallelic and biallelic mutations in MAB21L2 cause a spectrum of major eye malformations
    Joe Rainger
    Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, Edinburgh EH4 2XU, UK
    Am J Hum Genet 94:915-23. 2014
    ..The phenotype associated with the homozygous mutation might be a consequence of complete loss of MAB21L2 RNA binding, although the cellular function of this interaction remains unknown. ..
  5. ncbi request reprint Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome
    Kathleen A Williamson
    Medical Genetics Section, MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK
    Hum Mol Genet 15:1413-22. 2006
    ..SOX2, with NMYC and CHD7, is now the third transcriptional regulator known to be critical for normal oesophageal development in humans...
  6. pmc Heterozygous loss-of-function mutations in YAP1 cause both isolated and syndromic optic fissure closure defects
    Kathleen A Williamson
    Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
    Am J Hum Genet 94:295-302. 2014
    ..1066G>T mutation in family 132 should result in NMD in transcripts from either TSS. Amelioration of the phenotype by the alternative transcripts provides a plausible explanation for the phenotypic differences between the families...
  7. pmc Bilateral renal agenesis/hypoplasia/dysplasia (BRAHD): postmortem analysis of 45 cases with breakpoint mapping of two de novo translocations
    Louise Harewood
    MRC Human Genetics Unit, Institute of Genetic and Molecular Medicine, Edinburgh, United Kingdom
    PLoS ONE 5:e12375. 2010
    ..In the majority of cases, no specific etiology can be established, although teratogenic, syndromal and single gene causes can be assigned to some cases...
  8. pmc Disruption of SATB2 or its long-range cis-regulation by SOX9 causes a syndromic form of Pierre Robin sequence
    Jacqueline K Rainger
    MRC Human Genetics Unit, MRC Institute of Genetic and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
    Hum Mol Genet 23:2569-79. 2014
    ..This expression could be eliminated by mutating the SOX9-binding site of CRE2. These observations suggest that SATB2 and SOX9 may be acting together via complex cis-regulation to coordinate the growth of the developing jaw. ..
  9. doi request reprint 'Crommelin-type' symmetrical tetramelic reduction deformity: a new case and breakpoint mapping of a reported case with de-novo t(2;12)(p25.1;q23.3)
    Louise Harewood
    MRC Human Genetics Unit, Institute of Genetic and Molecular Medicine, Western General Hospital, Edinburgh EH4 2XU, UK
    Clin Dysmorphol 19:5-13. 2010
    ..We cannot assign a specific genetic mechanism in the translocation case but developmental disregulation of gene expression at one, or both, breakpoints may provide an explanation for the phenotype...
  10. doi request reprint Enhancer-adoption as a mechanism of human developmental disease
    Laura A Lettice
    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh
    Hum Mutat 32:1492-9. 2011
    ..This developmental genetic mechanism may explain a proportion of the novel or unexplained phenotypes associated with balanced chromosome rearrangements...
  11. pmc Anophthalmia and microphthalmia
    Amit S Verma
    MRC Human Genetics Unit, Edinburgh, UK
    Orphanet J Rare Dis 2:47. 2007
    ..The potential for visual development in microphthalmic patients is dependent upon retinal development and other ocular characteristics...
  12. pmc Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg Anophthalmia) syndrome in humans and mice
    Joe Rainger
    Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK
    PLoS Genet 7:e1002114. 2011
    ..Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice...
  13. pmc A trans-acting protein effect causes severe eye malformation in the Mp mouse
    Joe Rainger
    The MRC Human Genetics Unit, MRC Institute of Genetic and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
    PLoS Genet 9:e1003998. 2013
    ..The prediction of similar trans-acting protein effects will be an important challenge in the medical interpretation of human mutations from whole exome sequencing...
  14. doi request reprint A syndromic form of Pierre Robin sequence is caused by 5q23 deletions encompassing FBN2 and PHAX
    Morad Ansari
    MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
    Eur J Med Genet 57:587-95. 2014
    ..A possible critical region for TEV is distinct and telomeric to the PRS region. The molecular basis of PRS in these cases remains undetermined but haploinsufficiency for PHAX is a plausible mechanism...
  15. ncbi request reprint Mutations in SOX2 cause anophthalmia
    Judy Fantes
    MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK
    Nat Genet 33:461-3. 2003
    ..2) associated with bilateral anophthalmia. Subsequent SOX2 mutation analysis identified de novo truncating mutations of SOX2 in 4 of 35 (11%) individuals with anophthalmia. Both eyes were affected in all cases with an identified mutation...
  16. pmc Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism
    Morad Ansari
    MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
    J Med Genet 51:659-68. 2014
    ..Mutations in other cohesin components, SMC1A, SMC3, HDAC8 and RAD21 cause less typical CdLS...
  17. pmc Esrrg functions in early branch generation of the ureteric bud and is essential for normal development of the renal papilla
    Rachel Berry
    MRC Human Genetics Unit, Institute of Genetic and Molecular Medicine, Western General Hospital, Edinburgh EH4 2XU, UK
    Hum Mol Genet 20:917-26. 2011
    ..Taken together, these results suggest that Esrrg is required for early branching events of the ureteric duct that occur prior to the onset of nephrogenesis. These findings confirm ESRRG as a strong candidate gene for CAKUT...
  18. doi request reprint Miller (Genee-Wiedemann) syndrome represents a clinically and biochemically distinct subgroup of postaxial acrofacial dysostosis associated with partial deficiency of DHODH
    Joe Rainger
    MRC Human Genetics Unit, Institute of Genetic and Molecular Medicine, University of Edinburgh, Edinburgh, UK
    Hum Mol Genet 21:3969-83. 2012
    ..The developmental sensitivity to reduced pyrimidine synthesis capacity may reflect the requirement for an exceptional mitogenic response to growth factor signalling in the affected tissues...
  19. doi request reprint An atypical facial appearance and growth pattern in a child with Cornelia de Lange Syndrome: an intragenic deletion predicting loss of the N-terminal region of NIPBL
    Jennie E Murray
    South east Scotland Clinical Genetics Services Western General Hospital, Edinburgh, UK
    Clin Dysmorphol 21:22-3. 2012
    ..Herein we describe a patient with a rare intragenic deletion of NIPBL who has typical microcephaly and developmental problems but atypical growth pattern and facial features...
  20. ncbi request reprint Interstitial deletion of the long arm of chromosome 5 in a boy with multiple congenital anomalies and mental retardation: Molecular characterization of the deleted region to 5q22.3q23.3
    Sixto Garcia-Minaur
    South East of Scotland Genetics Service, Western General Hospital, Edinburgh, United Kingdom
    Am J Med Genet A 132:402-10. 2005
    ..Molecular studies need to be performed on these patients, to establish genotype-phenotype correlation and to understand the role and influence of genes in this region...
  21. doi request reprint The genetic architecture of microphthalmia, anophthalmia and coloboma
    Kathleen A Williamson
    Medical Research Council Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
    Eur J Med Genet 57:369-80. 2014
    ..Both the relative frequency of mutations in MAC cohort screens and the level of confidence in the assignment of disease-causing status were evaluated for each gene. ..
  22. pmc Variant detection sensitivity and biases in whole genome and exome sequencing
    Alison M Meynert
    MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, EH4 2XU Edinburgh, UK
    BMC Bioinformatics 15:247. 2014
    ..We set out to quantify and understand how WGS compares with the targeted capture and sequencing of the exome (exome-seq), for the specific purpose of identifying single nucleotide polymorphisms (SNPs) in exome targeted regions...
  23. ncbi request reprint Developmental eye disorders
    David R Fitzpatrick
    Medical Research Council, Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK
    Curr Opin Genet Dev 15:348-53. 2005
    ..This dialogue between clinical genetics and basic developmental biology provides a paradigm to enhance our understanding of many critical developmental processes in human embryogenesis...
  24. ncbi request reprint SOX2 anophthalmia syndrome
    Nicola K Ragge
    Adnexal Service, Moorfields Eye Hospital, London, United Kingdom
    Am J Med Genet A 135:1-7; discussion 8. 2005
    ....
  25. pmc Human-specific gain of function in a developmental enhancer
    Shyam Prabhakar
    Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Science 321:1346-50. 2008
    ....
  26. pmc Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation
    Francesca Pasutto
    Institute of Human Genetics, Friedrich Alexander University Erlangen Nuremberg, Erlangen, Germany
    Am J Hum Genet 80:550-60. 2007
    ..STRA6 mutations thus define a pleiotropic malformation syndrome representing the first human phenotype associated with mutations in a gene from the "STRA" group...
  27. pmc Evolutionarily conserved sequence elements that positively regulate IFN-gamma expression in T cells
    Maria Shnyreva
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 101:12622-7. 2004
    ..Like IFN-gamma expression, these histone modifications were T-bet-dependent in CD4+ cells, but not CD8+ T cells. These findings define two distal regulatory elements associated with T cell subset-specific IFN-gamma expression...
  28. ncbi request reprint Recurrence of SOX2 anophthalmia syndrome with gonosomal mosaicism in a phenotypically normal mother
    Laurence Faivre
    Centre de Genetique, Hôpital d Enfants, Dijon, France
    Am J Med Genet A 140:636-9. 2006
  29. pmc Heterozygous mutations of OTX2 cause severe ocular malformations
    Nicola K Ragge
    Department of Adnexal Surgery, Moorfields Eye Hospital, London, United Kingdom
    Am J Hum Genet 76:1008-22. 2005
    ..The high incidence of mosaicism and the reduced penetrance have implications for genetic counseling...
  30. ncbi request reprint Beckwith-Wiedemann-like macroglossia and 18q23 haploinsufficiency
    Frederic Lirussi
    Service de Biochime et Biologie Moléculaire, Hopital d Enfants Armand Trousseau, AP HP, Paris, France
    Am J Med Genet A 143:2796-803. 2007
    ..5. Because this minimal region of haplo-insufficiency falls into a common region of deletion in 18q- syndrome, we inferred that this macroglossia condition would follow a recessive pattern of inheritance...
  31. pmc Single-cell perforin and granzyme expression reveals the anatomical localization of effector CD8+ T cells in influenza virus-infected mice
    Barbara J Johnson
    Cooperative Research Centre for Vaccine Technology and Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Queensland 4029, Australia
    Proc Natl Acad Sci U S A 100:2657-62. 2003
    ..The data suggest that some CTL mature into perforin/granzyme-expressing effector cells in MLN but reach detectable frequencies only when they accumulate in the infected lung...
  32. ncbi request reprint Active recruitment of DNA methyltransferases regulates interleukin 4 in thymocytes and T cells
    Karen W Makar
    Department of Immunology, University of Washington, Seattle, Washington 98195, USA
    Nat Immunol 4:1183-90. 2003
    ..These results indicate that Dnmts, DNA and histone methylation, and transcription factors 'collaborate' to determine appropriate Il4 expression patterns...
  33. ncbi request reprint An excess of chromosome 1 breakpoints in male infertility
    Iben Bache
    Wilhelm Johannsen Centre for Functional Genome Research, Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Denmark
    Eur J Hum Genet 12:993-1000. 2004
    ..We suggest that chromosome 1 harbours a critical domain whose integrity is essential for male fertility...
  34. ncbi request reprint Methylation and demethylation in the regulation of genes, cells, and responses in the immune system
    David R Fitzpatrick
    Immunological Systems Department, Amgen Inc, 51 University St, Seattle, WA 98101, USA
    Clin Immunol 109:37-45. 2003
    ..The immune system is a fertile field for studies of epigenetic regulation of cell fate and function...
  35. pmc 3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome
    Lionel Willatt
    Department of Medical Genetics, Addenbrooke s Hospital, University of Cambridge, Cambridge, United Kingdom
    Am J Hum Genet 77:154-60. 2005
    ..The presence of two nearly identical low-copy repeat sequences in BAC clones on each side of the deletion breakpoint suggests that nonallelic homologous recombination is the likely mechanism of disease causation in this syndrome...
  36. pmc Medical sequencing of candidate genes for nonsyndromic cleft lip and palate
    Alexandre R Vieira
    Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
    PLoS Genet 1:e64. 2005
    ..This study also illustrates the need to test large numbers of controls to distinguish rare polymorphic variants and prioritize functional studies for rare point mutations...
  37. ncbi request reprint Role of SOX2 mutations in human hippocampal malformations and epilepsy
    Sanjay M Sisodiya
    Department of Clinical and Experimental Epilepsy, Institute of Neurology, UCL, London, and National Society for Epilepsy, Bucks SL90RJ, London, UK
    Epilepsia 47:534-42. 2006
    ..We wished to determine the underlying cerebral phenotype in SOX2 mutation and to test the candidacy of SOX2 as a gene contributing to human epilepsies...
  38. ncbi request reprint Rapid demethylation of the IFN-gamma gene occurs in memory but not naive CD8 T cells
    Ellen N Kersh
    Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Immunol 176:4083-93. 2006
    ....
  39. pmc CGG-repeat expansion in the DIP2B gene is associated with the fragile site FRA12A on chromosome 12q13.1
    Birgitta Winnepenninckx
    Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
    Am J Hum Genet 80:221-31. 2007
    ..These data suggest that deficiency of DIP2B, a brain-expressed gene, may mediate the neurocognitive problems associated with FRA12A...
  40. ncbi request reprint Inherited PAX6, NF1 and OTX2 mutations in a child with microphthalmia and aniridia
    R Alex Henderson
    Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, NE1 4LP, UK
    Eur J Hum Genet 15:898-901. 2007
    ..This case shows that patients with complex phenotypes should not be eliminated from subsequent mutation analysis after one or even two mutations are found...
  41. pmc Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing transcription of the gene encoding interferon-gamma
    Jamie R Schoenborn
    Department of Immunology, University of Washington, Seattle, Washington 98195, USA
    Nat Immunol 8:732-42. 2007
    ..Our findings suggest that proper expression of Ifng is maintained through the collective action of multiple distal regulatory elements present in a region of about 100 kilobases flanking Ifng...
  42. ncbi request reprint Murine plasmacytoid pre-dendritic cells generated from Flt3 ligand-supplemented bone marrow cultures are immature APCs
    Pierre Brawand
    Amgen Inc, Seattle, WA 98101, USA
    J Immunol 169:6711-9. 2002
    ..Thus, the in vitro generation of murine pDCs may serve as a useful tool to further investigate pDC biology as well as the potential role of these cells in viral immunity and other settings...