Tran Quynh Nhu
University of Tokyo, Japan
Title: Truncation and microdeletion of EVC accompanied by a novel EFCAB7 missense mutation in Ellis-Van Creveld syndrome with atypical congenital heart defect
Biography
Biography: Tran Quynh Nhu
Abstract
Ellis-van Creveld syndrome (EvC) is a ciliopathy with cardiac anomalies, disproportionate short stature, polydactyly, dystrophic nails and oral defects. Approximately 60% of EvC patients have severe congenital heart defects (CHD), of which more than half are atrio-ventricular septal defect and common atrium. In this study, we report one EvC Vietnamese family with an atypical CHD phenotype, short chordalis. A 32-month-old boy had a novel heterozygous EVC mutation (c.1717C>G-p.S572X) in exon 12, inherited from his father whose phenotype was milder than his son’s. Of note, the mother without an EvC phenotype showed a lower expression of EVC mRNA compared with controls. SNP array analysis revealed that the patient and mother had a heterozygous 16kb deletion in EVC, ranging from intron 9 to intron 11. As the patient and the father had an atypical CHD, we screened EFCAB7 and IQCE as the candidate for modifiers of EvC phenotype. EFCAB7 and IQCE are ciliary proteins, which positively regulate the Hh pathway and anchor the EVC-EVC2 complex in a signaling microdomain at the base of cilia. A novel missense mutation c.1171T>C-p.Y391H in EFCAB7 was found in the patient and the father. This mutation located in a possible binding site of EFCAB7 and EVC2, and may have modified the EvC phenotype in this family. Our findings suggested the physiological role of EFCAB7 in cardiac development.