Department of General Surgery, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China.
Department of Medical Information, School of Life Sciences, Central South University, Changsha, China.
Mol Genet Genomic Med. 2019 Sep;7(9):e885. doi: 10.1002/mgg3.885. Epub 2019 Jul 23.
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.
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.
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.
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.
Ellis-van Creveld 综合征（EVC）是一种非常罕见的遗传性骨骼发育不良，其临床特征为软骨发育不良、多指（趾）畸形、外胚层发育不良和心脏异常的四联征。本研究旨在鉴定一个五代同堂的汉族近亲婚配家系中 EVC 的遗传缺陷。
本研究纳入了一个五代 12 人的汉族家系。对先证者进行外显子组测序，以筛选潜在的遗传变异，然后对家系成员和 200 名无关的种族匹配对照进行 Sanger 测序以鉴定变异。
在患者中检测到 EVC 纤毛复合物亚单位 1 基因（EVC）中的 novel homozygous variant，c.2014C>T，p.(Q672*)，该变异与家系中的疾病共分离，在对照组中不存在。
该 novel homozygous EVC 变异，c.2014C>T，p.(Q672*)，导致了这个汉族家系中的 EVC。本研究中的发现扩展了 EVC 的突变谱，并可能为 EVC 的发病机制和诊断提供新的见解，具有遗传咨询和临床管理的意义。
