Mutations in Two Nonhomologous Genes in a Head-to-Head Configuration Cause Ellis-van Creveld Syndrome

Abstract

Ellis-van Creveld syndrome (EvC) is an autosomal recessive skeletal dysplasia. Elsewhere, we described mutations in EVC in patients with this condition (Ruiz-Perez et al. 2000). We now report that mutations in EVC2 also cause EvC. These two genes lie in a head-to-head configuration that is conserved from fish to man. Affected individuals with mutations in EVC and EVC2 have the typical spectrum of features and are phenotypically indistinguishable.

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.…”

Ellis-Van Creveld Syndrome: Radiological Findings of a Case and Review of the Literature

“…Polydactyly is always present and is seen as postaxial hexadactyly of the hands, and in 10% of the cases the feet. 3,8 Polydactyly is seen as a sixth finger at the ulnar side of the hands and may be in the form of extra soft tissue without cartilage, joint or tendon; or a complete formation of a digit with its own metacarpal and complete soft tissue.…”

“…8,9 However no mutations can be identified in either gene in 31% of the cases and more genetic research is needed to find out possibly further genetic heterogeneity. 9 Therefore practically the diagnosis of EVC syndrome is generally based on clinical grounds supported by radiological evaluation.…”