Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease  

作　　者：Noam Ben-Yosef Matthew Frampton Elena RSchiff Saleh Daher Fadi Abu Baker Rifaat Safadi Eran Israeli Anthony W.Segal Adam P.Levine 

机构地区：[1]Centre for Molecular Medicine,Division of Medicine,University College London,London,UK [2]Institute of Gastroenterology and Liver disease,Hadassah Medical Center,Jerusalem,Israel [3]Institute of Ophthalmology,Moorfields Eye Hospital,University College London,London,UK [4]Institue of Gastroenterology and Hepatology,Hillel Yaffe Medical Center,Hadera,Israel [5]Institute of Gastroenterology and Liver disease,E.Wolfson Medical Center,Holon,Israel [6]Department of Pathology,University College London,London,UK

出　　处：《Gastroenterology Report》2021年第6期521-532,共12页胃肠病学报道（英文）

基　　金：supported by the Charles Wolfson Charitable Trust and the Medical Research Council.

摘　　要：Background:Family studies support a genetic predisposition to inflammatory bowel diseases(IBD),but known genetic variants only partially explain the disease heritability.Families withmultiple affected individuals potentially harbour rare and highimpact causal variants.Long regions of homozygosity due to recent inbreedingmay increase the risk of individuals bearing homozygous loss-of-function variants.This study aimed to identify rare and homozygous genetic variants contributing to IBD.Methods:Four families with known consanguinity and multiple cases of IBD were recruited.In a family-specific analysis,we utilised homozygosity mapping complemented by whole-exome sequencing.Results:We detected a single region of homozygosity shared by Crohn’s disease cases from a family of Druze ancestry,spanning 2.6Mb containing the NOD2 gene.Whole-exome sequencing did not identify any potentially damaging variants within the region,suggesting that non-coding variation may be involved.In addition,affected individuals in the families harboured several rare and potentially damaging homozygous variants in genes with a role in autophagy and innate immunity including LRRK1,WHAMM,DENND3,and C5.Conclusion:This study examined the potential contribution of rare,high-impact homozygous variants in consanguineous families with IBD.While the analysis was not designed to achieve statistical significance,our findings highlight genes or loci that warrant further research.Non-coding variants affecting NOD2 may be of importance in Druze patients with Crohn’s disease.

关 键 词：inflammatory bowel disease family study GENETICS HOMOZYGOSITY 

分 类 号：R57[医药卫生—消化系统] R394[医药卫生—内科学]