Am J Med Genet 84:350–6ĭraper 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. Hum Genet 96:251–3ĭigilio MC, Marino B, Ammirati A, Borzaga U, Giannotti A, Dallapiccola B (1999) Cardiac malformations in patients with oral-facial-skeletal syndromes: clinical similarities with heterotaxia. Hum Mutat 11:1–3ĭigilio MC, Marino B, Giannotti A, Dallapiccola B (1995) Single atrium, atrioventricular canal/postaxial hexodactyly indicating Ellis–van Creveld syndrome. As we have not identified mutations in either gene in 20 cases (31%) it is possible that there is further genetic heterogeneity.Īntonarakis SE (1998) Recommendations for a nomenclature system for human gene mutations nomenclature working group. 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. The majority of the mutations introduce a premature termination codon. We have identified EVC2 mutations in 25 cases (38%) in 22 of these we have isolated a mutation on each allele. We have identified EVC mutations in 20 cases (31%) in all of these we have detected the mutation on each allele. We investigated mutations that could affect splicing by in vitro splicing assays and cDNA analysis. We PCR amplified and sequenced the coding exons of both genes.
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. Ellis–van Creveld syndrome (EvC) is caused by mutations in EVC and EVC2, genes in a divergent orientation separated by only 2.6 kb.