Identification of a novel EVC variant in a Han‐Chinese family with Ellis‐van Creveld syndrome

Abstract Background Ellis‐van Creveld syndrome (EVC), a very rare genetic skeletal dysplasia, is clinically characterized by a tetrad consisting of chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac anomalies. The aim of this study was to identify the genetic defect for EVC in a five‐generation consanguineous Han‐Chinese pedigree. Methods A five‐generation, 12‐member Han‐Chinese pedigree was enrolled in this study. Exome sequencing was applied in the proband to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in family members and 200 unrelated ethnicity‐matched controls. Results A novel homozygous variant, c.2014C>T, p.(Q672*), in the EvC ciliary complex subunit 1 gene (EVC), was detected in the patient, which was cosegregated with the disease in the family and absent in the controls. Conclusion The identified novel homozygous EVC variant, c.2014C>T, p.(Q672*), was responsible for EVC in this Han‐Chinese pedigree. The findings in this study extend the EVC mutation spectrum and may provide new insights into EVC causation and diagnosis with implications for genetic counseling and clinical management.