New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin

Liu, Xiaomin; Xu, Hanshi; Xu, Huaiqian; Geng, Qingshan; Mak, Wai-Ho; Ling, Fei; Su, Zheng; Yang, Fang; Zhang, Tao; Chen, Jiyan; Yang, Huanming; Wang, Jian; Zhang, Xiuqing; Xu, Xun; Jia, Huijue; Zhang, Zhiwei; Liu, Xiao; Zhong, Shilong

doi:10.1101/411165

Cited by 1 publication

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References 24 publications

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“…In fact, c.489G > A (p.Pro163=) (rs140410716) has been revealed as a disease modifier itself and has been associated with worse cardiac outcomes in a genome study of Han Chinese patients who had undergone STENT for acute coronary syndromes. Additionally, the study found lowered ECHS1 expression to be associated with a more severe clinical phenotype (Liu et al, 2018). Another study interested in genomic modifiers of coronary disease found a clear correlation of drug refractory dilated cardiomyopathy and several polymorphisms in ECHS1 (Campbell et al, 2018).…”

Section: Discussionmentioning

confidence: 92%

ECHS1 disease in two unrelated families of Samoan descent: Common variant ‐ rare disorder

Simon

Eftekharian

Ferdinandusse

et al. 2020

American J of Med Genetics Pt A

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Mutations in the short‐chain enoyl‐CoA hydratase (SCEH) gene, ECHS1, cause a rare autosomal recessive disorder of valine catabolism. Patients usually present with developmental delay, regression, dystonia, feeding difficulties, and abnormal MRI with bilateral basal ganglia involvement. We present clinical, biochemical, molecular, and functional data for four affected patients from two unrelated families of Samoan descent with identical novel compound heterozygous mutations. Family 1 has three affected boys while Family 2 has an affected daughter, all with clinical and MRI findings of Leigh syndrome and intermittent episodes of acidosis and ketosis. WES identified a single heterozygous variant in ECHS1 at position c.832G > A (p.Ala278Thr). However, western blot revealed significantly reduced ECHS1 protein for all affected family members. Decreased SCEH activity in fibroblasts and a mild increase in marker metabolites in urine further supported ECHS1 as the underlying gene defect. Additional investigations at the DNA (aCGH, WGS) and RNA (qPCR, RT‐PCR, RNA‐Seq, RNA‐Array) level identified a silent, common variant at position c.489G > A (p.Pro163=) as the second mutation. This substitution, present at high frequency in the Samoan population, is associated with decreased levels of normally spliced mRNA. To our understanding, this is the first report of a novel, hypomorphic allele c.489G > A (p.Pro163=), associated with SCEH deficiency.

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Section: Discussionmentioning

confidence: 92%