A novel missense mutation in obscurin gene in a Chinese consanguineous family with left ventricular noncompaction
Xue-Qi DONG1
Pei-Pei QIN2
Di ZHANG1
Qiong-Yu ZHANG1
Yi QU1
Lin ZHAO1
Yi-Ting LU1
Yu-Xiao HU1
Chun-Xue YANG1
Xin-Chang LIU1
Ya-Xin LIU1
Xian-Liang ZHOU1
1.Department of Cardiology,Fuwai Hospital,National Center for Cardiovascular Disease,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China2.Department of Obstetrics and Gynecology,Peking Union Medical College Hospital,Beijing,China
摘要：BACKGROUND Left ventricular noncompaction (LVNC) is an increasingly recognised cardiomyopathy of which a significant percentage are genetic in origin. The purpose of the present study was to identify potential pathogenic mutation leading to dis-ease in a Chinese LVNC family. METHODS A 3-generation family affected by LVNC was recruited. Clinical assessments were performed on available family members, with clinical examination, ECG, echocardiography and cardiac MRI. The proband (I-2), the proband's daughter (II-1, af-fected) and mother (III-1, unaffected) were selected for WGS. Sanger sequencing were performed in all of the 4 surviving family members. RESULTS Combined whole genome sequencing with linkage analysis identified a novel missense mutation in the giant protein obscurin (OBSCN NM_001098623, c.C19063T), as the only plausible disease-causing variant that segregates with disease among the four surviving individuals, with interrogation of the entire genome excluding other potential causes. This c.C19063T mis-sense mutation resulted in p.R6355W in the encoded OBSCN protein. It affected a highly conserved residue in the C terminus of the obscurin-B-like isoform between the PH and STKc domains, which was predicted to affect the function of the protein by dif-ferent bioinformatics tools. CONCLUSIONS Here we present clinical and genetic evidence implicating the novel R6355W missense mutation in obscurin as the cause of familial LVNC. This expands the spectrum of obscurin's roles in cardiomyopathies. It furthermore highlights that rare obscurin missense variants, currently often ignored or left uninterpreted, should be considered to be relevant for cardiomy-opathies and can be identified by the approach presented here. This study also provided new insights into the molecular basis of OBSCN mutation positive LVNC.
机标关键词：chinesemutationfamilynovelgenewithconsanguineousleft
论文发表日期：2022-07-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 531-538 )