Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis–van Creveld syndrome patients
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Ellis–van Creveld syndrome (EvC) is caused by mutations in EVC and EVC2, genes in a divergent orientation separated by only 2.6 kb. We systematically sought mutations in both genes in a panel of 65 affected individuals to assess the proportion of cases resulting from mutations in each gene. We PCR amplified and sequenced the coding exons of both genes. We investigated mutations that could affect splicing by in vitro splicing assays and cDNA analysis. We have identified EVC mutations in 20 cases (31%); in all of these we have detected the mutation on each allele. We have identified EVC2 mutations in 25 cases (38%); in 22 of these we have isolated a mutation on each allele. The majority of the mutations introduce a premature termination codon. We sequenced the region between the two genes in 10 of the 20 cases in which we had not identified a mutation in either gene, revealing only one SNP that was not a common polymorphism. As we have not identified mutations in either gene in 20 cases (31%) it is possible that there is further genetic heterogeneity.
KeywordsEpidermolysis Bullosa Premature Termination Codon Bardet Biedl Syndrome Missense Change Atrioventricular Septal Defect
This work was funded by the British Heart Foundation and European Commission (QLG1-2001-02188). We would like to acknowledge all clinicians that sent us samples for screening.
- Draper N, Walker EA, Bujalska IJ, Tomlinson JW, Chalder SM, Arlt W, Lavery GG, Bedendo O, Ray DW, Laing I, Malunowicz E, White PC, Hewison M, Mason PJ, Connell JM, Shackleton CH, Stewart PM (2003) Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. Nat Genet 34:434–9PubMedCrossRefGoogle Scholar
- Ellis RWB, van Creveld S (1940) A syndrome characterised by ectodermal dysplasia, polydactyly, chondro-dysplasia and congenital morbus cordis: report of three cases. Arch Dis Child 15:65–84Google Scholar
- McIntosh (1933) In: Holt, Howland (eds) Diseases of infancy and childhood, 10th edn Appleton-Century-Crofts, New York, pp 362Google Scholar
- Ruiz-Perez VL, Ide SE, Strom TM, Lorenz B, Wilson D, Woods K, King L, Francomano C, Freisinger P, Spranger S, Marino B, Dallapiccola B, Wright M, Meitinger T, Polymeropoulos MH, Goodship J (2000) Mutations in a new gene in Ellis–van Creveld syndrome and Weyers acrodental dysostosis. Nat Genet 24:283–6PubMedCrossRefGoogle Scholar
- Savage DB, Agostini M, Barroso I, Gurnell M, Luan J, Meirhaeghe A, Harding AH, Ihrke G, Rajanayagam O, Soos MA, George S, Berger D, Thomas EL, Bell JD, Meeran K, Ross RJ, Vidal-Puig A, Wareham NJ, O’Rahilly S, Chatterjee VK, Schafer AJ (2002) Digenic inheritance of severe insulin resistance in a human pedigree. Nat Genet 31:379–84PubMedGoogle Scholar
- Wallace AJ (2003) Mutation scanning for the clinical laboratory: automated fluorescent sequencing. In: Elles R, Mountford R (eds) Molecular diagnosis of genetic diseases, 2nd edn Humana press, pp 81–114Google Scholar