title: Exome Sequencing in a Family Identifies RECQL5 Mutation Resulting in Early Myocardial Infarction.
abstract: Coronary artery disease (CAD) including myocardial infarction (MI) is the leading cause of death worldwide and is commonly caused by the interaction between genetic factors and environmental risks. Despite intensive efforts using linkage and candidate gene approaches, the genetic etiology for the majority of families with a multigenerational early CAD /MI predisposition is unknown.In this study, we used whole-exome sequencing of 10 individuals from 1 early MI family, in which 4 siblings were diagnosed with MI before the age of 55, to identify potential predisposing genes.We identified a mutation in the RECQL5 gene, 1 of the 5 members of the RECQ family which are involved in the maintenance of genomic stability. This novel mutation, which is a TG insert at position 73,626,918 on the 13 chromosome and occurs before the last nucleotide of the introns 11 acceptor splice site affecting splicing of RECQL5. RT-PCR suggested the control subject had a full-length mRNA including exon 12, but the patients with RECQL5 mutation had a shorter mRNA form involving splicing of exons 11 to 13 directly, with skipping of exon 12. Quantitative RT-PCR analysis of RECQL5 exon 12 demonstrated that individuals whose genotype is mutant homozygote had only trace amounts of mRNA containing this exon and the family members who carry the heterozygous genotype had a level at 48% to 55% of the control's level.These findings provide insight into both the pathogenesis of MI and the role of RECQL5 gene in human disease.
authors: From the Department of Coronary Artery Disease, Heart Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, PR China.
authors: Xiang
authors: X
authors: Xie
authors: Ying-Ying
authors: YY
authors: Zheng
authors: Dilare
authors: D
authors: Adi
authors: Yi-Ning
authors: YN
authors: Yang
authors: Yi-Tong
authors: YT
authors: Ma
authors: Xiao-Mei
authors: XM
authors: Li
authors: Zhen-Yan
authors: ZY
authors: Fu
authors: Xiang
authors: X
authors: Ma
authors: Fen
authors: F
authors: Liu
authors: Zi-Xiang
authors: ZX
authors: Yu
authors: You
authors: Y
authors: Chen
authors: Ying
authors: Y
authors: Huang
mesh_terms: D059472:Exome; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009203:Myocardial Infarction / Q000235:genetics*; D053484:RecQ Helicases / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C506732:RECQL5 protein, human; D053484:RecQ Helicases