Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis

Abstract

Ellis-van Creveld syndrome (EvC, MIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals. The disease was mapped to chromosome 4p16 in nine Amish subpedigrees and single pedigrees from Mexico, Ecuador and Brazil. Weyers acrodental dysostosis (MIM 193530), an autosomal dominant disorder with a similar but milder phenotype, has been mapped in a single pedigree to an area including the EvC critical region. We have identified a new gene (EVC), encoding a 992-amino-acid protein, that is mutated in individuals with EvC. We identified a splice-donor change in an Amish pedigree and six truncating mutations and a single amino acid deletion in seven pedigrees. The heterozygous carriers of these mutations did not manifest features of EvC. We found two heterozygous missense mutations associated with a phenotype, one in a man with Weyers acrodental dysostosis and another in a father and his daughter, who both have the heart defect characteristic of EvC and polydactyly, but not short stature. We suggest that EvC and Weyers acrodental dysostosis are allelic conditions.

Smoothened transduces Hedgehog signal by forming a complex with Evc/Evc2

“…EVC and EVC2 are adjacent genes identified in the recessive skeletal dysplasia Ellis-van Creveld syndrome (EvC; MIM: 225500), and loss-of-function mutation in either gene leads to the same condition [31][32][33][34]. Recent studies indicate that Evc promotes chondrocyte proliferation, hypertrophy and the differentiation of osteoblasts in the perichondrium, and localizes to the primary cilia of osteoblasts to mediate Hh signaling in the osteoblast lineage [35].…”

Ellis—van Creveld Syndrome with Sagittal Craniosynostosis

“…10 Mutations in the EVC1 and EVC2 genes have been found in approximately twothirds of the EVC cases. 5,6 No known mutation has been identified in the other one-third. 7 In this case, the patient and his older sister both carried a clinical diagnosis of the EVC, without mutation in either EVC1 or EVC2.…”

“…1 Since then, only 300 cases reported as of 2000. 5 The incidence is estimated at around 7/1,000,000. 2 The condition is more common among the American Amish, but it is known to affect all races with equal sex predilection.…”

Renal Transplant in an Adult with Ellis Van Creveld Syndrome: A Case Report and Literature Review

“…The EVC underlying gene was mapped to chromosome 4p16 [5] and mutations have been found in the EVC gene by Ruiz-Perez et al [2]. Mutations in a second gene EVC2, which is arranged in a head to head configuration with the EVC gene on chromosome 4, have also been identified as causative of the disease in a number of patients [6].…”

“…It is a relatively rare disorder but seems more common in the Amish population of United State of America and some Arab populations [2][3][4].…”