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Genomes and Genes | A O WilkieSummaryAffiliation: University of Oxford Country: UK Publications
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Publications
Why study human limb malformations?Andrew O M Wilkie
Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK
J Anat 202:27-35. 2003....
FGFs, their receptors, and human limb malformations: clinical and molecular correlationsAndrew O M Wilkie
Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
Am J Med Genet 112:266-78. 2002..A further test of this hypothesis is provided by a unique family segregating two FGFR2 mutations in cis (S252L; A315S), in which severe syndactyly occurs in the absence of the craniosynostosis that typically accompanies FGFR2 mutations...- Genetics of craniofacial development and malformationA O Wilkie
Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford OX3 9DS, UK
Nat Rev Genet 2:458-68. 2001..Many of these disorders have their origins in specific embryological processes, including abnormalities of brain patterning, of the migration and fusion of tissues in the face, and of bone differentiation in the skull vault... - Expression patterns of Twist and Fgfr1, -2 and -3 in the developing mouse coronal suture suggest a key role for twist in suture initiation and biogenesisD Johnson
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK
Mech Dev 91:341-5. 2000..Twist expression domains show some overlap with those of Fgfr2, which is expressed in the most immature (proliferating) osteogenic tissue... - Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndromeA O Wilkie
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK
Nat Genet 9:165-72. 1995..The contrasting effects of these mutations provide a genetic resource for dissecting the complex effects of signal transduction through FGFRs in cranial and limb morphogenesis... - Craniosynostosis and related limb anomaliesA O Wilkie
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK
Novartis Found Symp 232:122-33; discussion 133-43. 2001..DNA binding studies show that the craniosynostosis and parietal foramina arise from gain and loss of function, respectively... - A survey of TWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individualsN Elanko
Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford, UK
Hum Mutat 18:535-41. 2001..The glycine stretch may serve as a flexible linker between the functional domains of the TWIST protein, and as such may be subject to reduced evolutionary constraint... - A novel mutation, Ala315Ser, in FGFR2: a gene-environment interaction leading to craniosynostosis?D Johnson
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK
Eur J Hum Genet 8:571-7. 2000..To our knowledge, this is the first report of an interaction between a weakly pathogenic mutation and intrauterine constraint, leading to craniosynostosis... - Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossificationA O Wilkie
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK
Nat Genet 24:387-90. 2000.... - Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defectsL A Mavrogiannis
Institute of Molecular Medicine, The John Radcliffe, Headington, Oxford, UK
Nat Genet 27:17-8. 2001..Here we identify ALX4, which encodes a paired-related homeodomain transcription factor, as the PFM disease gene in P11pDS... - Exclusive paternal origin of new mutations in Apert syndromeD M Moloney
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK
Nat Genet 13:48-53. 1996..This identifies the biological basis of the paternal age effect for new mutations previously suggested for this disorder... - Linkage of otopalatodigital syndrome type 2 (OPD2) to distal Xq28: evidence for allelism with OPD1S P Robertson
Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom
Am J Hum Genet 69:223-7. 2001..8-2.1 Mb. We also demonstrate that female carriers of this disorder exhibit skewed inactivation that segregates with the high-risk haplotype and may be inversely related to the severity with which they manifest features of the disorder... - Prevalence of Pro250Arg mutation of fibroblast growth factor receptor 3 in coronal craniosynostosisD M Moloney
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK
Lancet 349:1059-62. 1997..We aimed to find out the proportion of cases of apparently non-syndromic coronal craniosynostosis attributable to this mutation... - Fgfr2 and osteopontin domains in the developing skull vault are mutually exclusive and can be altered by locally applied FGF2S Iseki
Department of Human Anatomy, Oxford, UK
Development 124:3375-84. 1997.... - Characterisation of the human snail (SNAI1) gene and exclusion as a major disease gene in craniosynostosisS R Twigg
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK
Hum Genet 105:320-6. 1999..Two single nucleotide polymorphisms encoding synonymous amino acids were identified in exon 2. The SNAI1P pseudogene was isolated, sequenced and mapped to chromosome band 2q34... - Genotype-phenotype correlation for nucleotide substitutions in the IgII-IgIII linker of FGFR2M Oldridge
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
Hum Mol Genet 6:137-43. 1997..The description of independent, complex nucleotide substitutions involving identical nucleotides is unprecedented, and we speculate that this may result from functional selection of FGFR mutations in sperm... - Mutational analysis in X-linked spondyloepiphyseal dysplasia tardaP T Christie
Molecular Endocrinology Group, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DU, United Kingdom
J Clin Endocrinol Metab 86:3233-6. 2001..The results of our study expand the spectrum of SEDLIN mutations associated with SEDT, and this will help to elucidate further the role of this novel protein in the etiology of this form of osteochondrodysplasia... - Conserved use of a non-canonical 5' splice site (/GA) in alternative splicing by fibroblast growth factor receptors 1, 2 and 3S R Twigg
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK
Hum Mol Genet 7:685-91. 1998..Inclusion or exclusion of the Val-Thr dipeptide may play an important role in controlling FGFR signalling through the Ras/MAPK pathway... - Dominant mutations in ROR2, encoding an orphan receptor tyrosine kinase, cause brachydactyly type BM Oldridge
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
Nat Genet 24:275-8. 2000..Expression of the mouse mouse orthologue, Ror2, early in limb development indicates that BDB arises as a primary defect of skeletal patterning... - Craniosynostosis: genes and mechanismsA O Wilkie
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
Hum Mol Genet 6:1647-56. 1997.... - Brachydactyly type B: linkage to chromosome 9q22 and evidence for genetic heterogeneityM Oldridge
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom
Am J Hum Genet 64:578-85. 1999..These results enable a refined classification of BDB and identify a novel locus for digit morphogenesis in 9q22... - Newly recognised craniosynostosis syndrome that does not map to known disease lociE M Blair
Department of Clinical Genetics, Oxford Radcliffe Hospital NHS Trust, The Churchill, United Kingdom
Am J Med Genet 95:4-9. 2000..Given the clinical novelty and parental consanguinity, we hypothesise that the affected individuals were autozygous for a recessively inherited mutation, at a novel locus, predisposing to craniosynostosis... - Mutations in the third immunoglobulin domain of the fibroblast growth factor receptor-2 gene in Crouzon syndromeM Oldridge
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK
Hum Mol Genet 4:1077-82. 1995..The first deletion within an FGFR gene is reported. Together with mutations in exon IIIc these account for 25 mutations out of 40 Crouzon patients studied in our combined series (5)... - X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysisR J Gibbons
MRC Molecular Haematology Unit, John Radcliffe Hospital, Oxford, U K
Am J Hum Genet 51:1136-49. 1992..Furthermore, they represent an important step in developing strategies to understand how the mutant ATR-X allele causes mental handicap, dysmorphism, and down-regulation of the alpha-globin genes... - A truncated human chromosome 16 associated with alpha thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)nA O Wilkie
MRC Molecular Haematology Unit, John Radcliffe Hospital, Headington, Oxford, UK
Nature 346:868-71. 1990..The mutation is stably inherited, proving that telomeric DNA alone is sufficient to stabilize the broken chromosome end. This mechanism may occur in any genetic disease associated with chromosome truncation... - Localisation of human alpha globin to 16p13.3----pterV J Buckle
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford
J Med Genet 25:847-9. 1988..13----qter. DNA studies show that the patient has not inherited either maternal alpha globin allele. This accounts for the alpha thalassaemia trait in the child and places the human alpha globin complex in band 16p13.3----pter... - Enlarged parietal foramina caused by mutations in the homeobox genes ALX4 and MSX2: from genotype to phenotypeLampros A Mavrogiannis
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
Eur J Hum Genet 14:151-8. 2006..Mutation screening has a high pickup rate in PFM, especially in familial cases, but is not indicated in CRS... - Growth of the normal skull vault and its alteration in craniosynostosis: insights from human genetics and experimental studiesGillian M Morriss-Kay
Department of Human Anatomy and Genetics, University of Oxford, UK
J Anat 207:637-53. 2005.... - Fibroblast growth factor receptor 2, gain-of-function mutations, and tumourigenesis: investigating a potential linkRuth M S Hansen
Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, UK
J Pathol 207:27-31. 2005..This suggests that gain-of-function FGFR2 mutations are not commonly encountered in tumourigenesis and specifically excludes a major contribution in testicular tumours... - Bad bones, absent smell, selfish testes: the pleiotropic consequences of human FGF receptor mutationsAndrew O M Wilkie
Weatherall Institute of Molecular Medicine, NDCLS, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK
Cytokine Growth Factor Rev 16:187-203. 2005..These clinical observations illustrate the pleiotropism of FGFR action and fuel ongoing efforts to understand the rich biology and pathophysiology of the FGF signalling system... - Gain-of-function amino acid substitutions drive positive selection of FGFR2 mutations in human spermatogoniaAnne Goriely
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
Proc Natl Acad Sci U S A 102:6051-6. 2005..Among FGFR2 mutations, those causing Apert syndrome may be especially prevalent because they enhance signaling by FGF ligands specific for each of the major expressed isoforms... 
Implications of a vertex bulge following modified strip craniectomy for sagittal synostosisDamian D Marucci
Oxford Craniofacial Unit and the Department of Plastic and Reconstructive Surgery, West Wing, John Radcliffe Hospital, Oxford, United Kingdom
Plast Reconstr Surg 122:217-24. 2008..The authors assessed the significance of the development of a progressive vertex bulge following strip craniectomy as a predictor of raised intracranial pressure or multiple suture synostosis...- Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosisAmy E Merrill
Department of Biochemistry and Molecular Biology, Norris Cancer Hospital, University of Southern Califoirnia Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089 0176, USA
Hum Mol Genet 15:1319-28. 2006..This provides genetic evidence that Twist1, Msx2 and Efna4 function together in boundary formation and the pathogenesis of coronal synostosis... - Clinical dividends from the molecular genetic diagnosis of craniosynostosisAndrew O M Wilkie
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
Am J Med Genet A 140:2631-9. 2006..In particular, the difficulty of analyzing the complex interaction of genetic background and prenatal environment in determining clinical features, limits the value of identifying low penetrance mutations... - Clinical dividends from the molecular genetic diagnosis of craniosynostosisAndrew O M Wilkie
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
Am J Med Genet A 143:1941-9. 2007..In particular, the difficulty of analyzing the complex interaction of genetic background and prenatal environment in determining clinical features, limits the value of identifying low penetrance mutations... - Nonsense-mediated decay and the molecular pathogenesis of mutations in SALL1 and GLI3Dominic Furniss
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
Am J Med Genet A 143:3150-60. 2007..c) 2007 Wiley-Liss, Inc... - Polydactyly in the mouse mutant Doublefoot involves altered Gli3 processing and is caused by a large deletion in cis to Indian hedgehogChristian Babbs
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK
Mech Dev 125:517-26. 2008..The large deletion interval may explain the wide range of abnormalities in Dbf/(+) mutants. However, we did not detect anologous deletions in cases of Laurin-Sandrow syndrome, a human disorder that shows phenotypic similarities to Dbf... - A variant in the sonic hedgehog regulatory sequence (ZRS) is associated with triphalangeal thumb and deregulates expression in the developing limbDominic Furniss
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK
Hum Mol Genet 17:2417-23. 2008..Depending on the dispersal of the founding mutation, it may play a wider role in the aetiology of this disorder... - A further mutation of the FGFR2 tyrosine kinase domain in mild Crouzon syndromeThomy J L de Ravel
Center for Human Genetics, UZ Gasthuisberg, KU Leuven, Leuven, Belgium
Eur J Hum Genet 13:503-5. 2005..Our observations expand both the clinical and molecular spectrum of this unusual subset of FGFR2 mutations... - Skeletal development is regulated by fibroblast growth factor receptor 1 signalling dynamicsMohammad K Hajihosseini
School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Development 131:325-35. 2004.... - Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ lineAnne Goriely
Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK
Science 301:643-6. 2003..We propose that these FGFR2 mutations, although harmful to embryonic development, are paradoxically enriched because they confer a selective advantage to the spermatogonial cells in which they arise... - Abnormal spliceform expression associated with splice acceptor mutations in exon IIIc of FGFR2Andrew O M Wilkie
Am J Med Genet 111:105. 2002 - Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosisShih hsin Kan
Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Oxford, United Kingdom
Am J Hum Genet 70:472-86. 2002..We conclude that the spectrum of FGFR2 mutations causing craniosynostosis is wider than previously recognized but that, nevertheless, the IgIIIa/IIIc region represents a genuine mutation hotspot... - Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndromeStephen R F Twigg
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
Proc Natl Acad Sci U S A 101:8652-7. 2004..This is the only known mutation in the ephrin/Eph receptor signaling system in humans and provides clues to the biogenesis of craniosynostosis... - Alx4 and Msx2 play phenotypically similar and additive roles in skull vault differentiationIleana Antonopoulou
Department of Human Anatomy and Genetics, University of Oxford, Oxford, UK
J Anat 204:487-99. 2004.... - Paternal origin of FGFR3 mutations in Muenke-type craniosynostosisSahan V Rannan-Eliya
NDCLS, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Headington, Oxford, UK
Hum Genet 115:200-7. 2004..We conclude that similar biological processes are likely to shape the occurrence of this c.749C>G mutation as for other mutations of FGFR3 as well as FGFR2... - An acceptor splice site mutation in HOXD13 results in variable hand, but consistent foot malformationsShih hsin Kan
Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
Am J Med Genet A 121:69-74. 2003..1998: Am. J. Hum. Genet. 63: 992-1000] in which different deletions of HOXD13 were reported. These findings together lend support to a distinct phenotype resulting from haploinsufficiency of HOXD13... - RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesityDagan Jenkins
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
Am J Hum Genet 80:1162-70. 2007.... - A new locus for split hand/foot malformation with long bone deficiency (SHFLD) at 2q14.2 identified from a chromosome translocationChristian Babbs
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
Hum Genet 122:191-9. 2007..2 breakpoint associated with ectrodactyly, and the mapping of the ectrodactylous Dominant hemimelia mouse mutation to a region of homologous synteny, suggests that 2q14.2 represents a novel locus for SHFLD... - Missense mutations in the homeodomain of HOXD13 are associated with brachydactyly types D and EDavid Johnson
Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, and Department of Plastic and Reconstructive Surgery, Radcliffe Infirmary, Oxford, United Kingdom
Am J Hum Genet 72:984-97. 2003..Molecular modeling of the Ile314Leu mutation indicates that this mixed gain and loss of affinity may be accounted for by the relative positions of methyl groups in the amino acid side chain and target base... - Cancer drugs to treat birth defectsAndrew O M Wilkie
Nat Genet 39:1057-9. 2007 - Monozygotic twins discordant for frontonasal malformationShehla N Mohammed
Department of Clinical Genetics, Guy's Hospital, London, United Kingdom
Am J Med Genet A 130:384-8. 2004..Monozygosity of all five twin pairs was confirmed, and the clinical features were reviewed. We discuss the mechanistic relationship between FNM and the twinning process and the genetic implications of this association... - Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humansStephen P Robertson
Weatherall Institute of Molecular Medicine, Room 304, The John Radcliffe, Headley Way, Oxford OX3 9DS, UK
Nat Genet 33:487-91. 2003.... - Efficient use of a 'dead-end' GA 5' splice site in the human fibroblast growth factor receptor genesSimon Brackenridge
Nuffield Department of Medicine, John Radcliffe Hospital, Oxford University, Oxford OX3 9DS, UK
EMBO J 22:1620-31. 2003..Thus the GA 5' splice site represents an extension of the adjacent conventional 5' splice site, the first natural example of such a composite 5' splice site... - Frontometaphyseal dysplasia: mutations in FLNA and phenotypic diversityStephen P Robertson
Department of Paediatrics and Child Health, Dunedin School of Medicine, Dunedin, New Zealand
Am J Med Genet A 140:1726-36. 2006..This observation suggests that locus heterogeneity may exist for this disorder... - The origin of EFNB1 mutations in craniofrontonasal syndrome: frequent somatic mosaicism and explanation of the paucity of carrier malesStephen R F Twigg
Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, United Kingdom
Am J Hum Genet 78:999-1010. 2006..These results highlight the importance of considering possible origins of mutation in the counseling of families with CFNS and provide a generally applicable approach to the combined analysis of mosaic and germline mutations... - Expanding the phenotype of craniofrontonasal syndrome: two unrelated boys with EFNB1 mutations and congenital diaphragmatic herniaPradeep C Vasudevan
Department of Clinical Genetics, Sheffield Children s Hospital, Sheffield, South Yorkshire, UK
Eur J Hum Genet 14:884-7. 2006..Our cases represent the first in which CDH has been confirmed in males with mutations in EFNB1, highlighting an important role for signalling by ephrin-B1 in the development of the diaphragm... - Postzygotic mutation and germline mosaicism in the otopalatodigital syndrome spectrum disordersStephen P Robertson
Department of Paediatrics and Child Health, Dunedin School of Medicine, Otago University, Dunedin, New Zealand
Eur J Hum Genet 14:549-54. 2006..The description of somatic mutations and germline mosaicism in FLNA has implications for clinical and molecular diagnosis, phenotypic expression and genetic counseling of families with these disorders... - Parietal foramina with cleidocranial dysplasia is caused by mutation in MSX2Sixto Garcia-Minaur
South East Scotland Genetic Service, Western General Hospital, Edinburgh, UK
Eur J Hum Genet 11:892-5. 2003..Our observations highlight the role of MSX2 in clavicular development and the importance of radiological examination of the clavicles in subjects with PFM... - Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCORDavid Ng
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
Nat Genet 36:411-6. 2004.... - FGFR3 P250R mutation increases the risk of reoperation in apparent 'nonsyndromic' coronal craniosynostosisGregory P L Thomas
Oxford Craniofacial Unit, Radcliffe Infirmary, Oxford, United Kingdom
J Craniofac Surg 16:347-52; discussion 353-4. 2005..3%) without the mutation. This highlights the need for genetic analysis and long-term clinical follow-up in apparently "isolated" coronal synostosis... - Functional analysis of natural mutations in two TWIST protein motifsNoriko Funato
Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan
Hum Mutat 25:550-6. 2005..This analysis further dissects the structure-function relationships of TWIST and corroborates with phenotypic observations of disease expressivity... - Mutational screening of FGFR1, CER1, and CDON in a large cohort of trigonocephalic patientsFernanda Sarquis Jehee
Centro de Estudos do Genoma Humano, Departamento de Biologia, , , , , SP, Brazil
Cleft Palate Craniofac J 43:148-51. 2006..Screening of FGFR1 (exon 7) for diagnostic purposes should not be performed in trigonocephalic patients...