Ellis-van Creveld syndrome and profound deafness resulted by sequence variants in the EVC/EVC2 and TMC1 genes

Ellis-van Creveld syndrome is an autosomal recessive skeletal dysplasia primarily characterized by the features such as disproportionate dwarfism, short ribs, short limbs, dysplastic nails, cardiovascular malformations, post-axial polydactyly (PAP) (bilateral) of hands and feet. EVC/EVC2 located in head-to-head arrangement on chromosome 4p16 are the causative genes for EvC syndrome. In the study, we present two families, A and B, with Pakistani and Republic of Kosovo origin, respectively. They showed features of EvC syndrome and were clinically and genetically characterized. In family A, the affected members showed an additional feature of profound deafness. The whole exome sequencing (WES) in this family revealed two homozygous variants in EVC2 (c.30dupC; p.Thr11Hisfs*45) and TMC1 (c.1696-1G>A) genes. In family B, WES revealed novel compound heterozygous variants (p.Ser307Pro, c.2894+3A>G) in the EVC gene. This study reports first case of variants in the genes causing EvC syndrome and profound deafness in the same family.