外显子组测序
PCSK9
家族性高胆固醇血症
外显子组
遗传学
突变
低密度脂蛋白受体
医学
人口
生物
基因
生物信息学
内科学
胆固醇
脂蛋白
环境卫生
作者
Krishna Kumar B. Pillai,Swarup A V Shah,Lakshmi Lavanya Reddy,Tester F. Ashavaid,Sunitha Vishwanathan
标识
DOI:10.1016/j.cca.2021.12.022
摘要
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder with elevated LDL-C levels which can ultimately lead to premature Coronary Artery Disease (CAD).In presence of limited genetic data on FH in India, the present study was aimed to determine the mutation spectrum in Indian FH patients using a targeted exome sequencing.54 FH cases (31 index cases + 23 extended family members) were categorized according to Dutch Lipid Clinic Network Criteria (DLCNC). Targeted exome sequencing was performed using 23 gene panel associated with lipid metabolism.All subjects showed the presence of family history of CAD, 38(70%) patients had corneal arcus whereas only 06(11%) subjects had xanthomas. As per the DLCNC, definite, probable, possible and unlikely FH were 48%, 30%, 11% and 11% respectively. Mutations were observed in 12 of the 23 gene panel with CETP, APOA5, EPHX2 and SREBP2 genes were identified for the first time in Indian FH patients. All 19 mutations including a novel frame-shift mutation in LDLR gene were reported for the first time in Indian FH patients. These mutations were identified in 28(52%) subjects and interestingly ∼73% of the clinically identified FH patients didn't harbour mutations in FH classical genes (LDLR, ApoB, PCSK9).This is the first study in the South Indian FH patients to perform targeted exome sequencing. Absence of mutations in the FH classical genes strongly indicates the polygenic nature of FH, further underscoring the importance of targeted exome sequencing for identifying mutations in genetically diverse Indian population.
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