Isolated X-Linked Hypertrophic Cardiomyopathy Caused by a Novel Mutation of the Four-and-a-Half LIM Domain 1 Gene

Author:

Hartmannova Hana1,Kubanek Milos1,Sramko Marek1,Piherova Lenka1,Noskova Lenka1,Hodanova Katerina1,Stranecky Viktor1,Pristoupilova Anna1,Sovova Jana1,Marek Tomas1,Maluskova Jana1,Ridzon Petr1,Kautzner Josef1,Hulkova Helena1,Kmoch Stanislav1

Affiliation:

1. From the Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic (H.H., L.P., L.N., K.H., V.S., A.P., J.S., H.H., S.K.); Departments of Cardiology (M.K., M.S., T.M., J.K.) and Pathology (J.M.), Institute for Clinical and Experimental Medicine, Prague, Czech Republic; and Department of Neurology, Thomayer’s Hospital, Prague, Czech Republic (P.R.).

Abstract

Background— Hypertrophic cardiomyopathy with severe left ventricular diastolic dysfunction has been associated with marked exercise intolerance and poor prognosis. However, molecular pathogenesis of this phenotype remains unexplained in a large proportion of cases. Methods and Results— We performed whole exome sequencing as an initial genetic test in a large Czech family with 3 males affected by nonobstructive hypertrophic cardiomyopathy with severe left ventricular diastolic dysfunction in end-stage disease. A novel frameshift mutation of four-and-a-half LIM domain 1 gene ( FHL1 ) (c.599_600insT; p.F200fs32X) was detected in these individuals. The mutation does not affect transcription, splicing, and stability of FHL1 mRNA and results in production of truncated FHL1 protein, which is contrary to heart tissue homogenate not detectable in frozen tissue sections of myocardial biopsy of affected males. The identified mutation cosegregated also with abnormal ECG and with 1 case of apical hypertrophic cardiomyopathy in heterozygous females. Although skeletal muscle involvement is a common finding in FHL1-related diseases, we could exclude myopathy in all mutation carriers. Conclusions— We identified a novel FHL1 mutation causing isolated hypertrophic cardiomyopathy with X-chromosomal inheritance.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Genetics(clinical),Cardiology and Cardiovascular Medicine,Genetics

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3