与NRAP基因纯合截断变异相关的扩张型心肌病外显率降低和可变表达。

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Aisha Alqahtani, Sahar Tulbah, Nadiah Alruwaili, Saud Takroni, Maarab Alkorashy, Waleed Manea, Dimpna C Albert Brotons, Abdullah Alwadai, Jehad Alburaiki, Fowzan Alkuraya, Nadiah Al-Hashmi, Samah Zarroug, Zuhair N Al-Hassnan
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引用次数: 0

摘要

扩张型心肌病(DCM)是一种遗传异质性的左心室扩张和收缩功能障碍,导致心力衰竭。它主要以显性模式遗传。隐性遗传很少遇到。本研究旨在概述与我们高度近亲人群中隐性遗传NRAP截断变异相关的临床和遗传特征。23例病例来自12个无血缘关系的近亲家庭。所有病例均进行心脏病学评估和外显子组测序(ES)基因检测,然后进行一级亲属分离分析。遗传分析鉴定出5个独特的纯合截断变异。分离分析共检测到23个纯合个体和21个杂合个体。在全部纯合子病例中,3例无症状,而20例表现出症状,其发病年龄在家族间和家族内具有显著差异(范围:9个月至47岁,中位10年),其中7例死亡(范围:9个月至28岁,中位7年)。杂合子个体均未出现症状。值得注意的是,有3例纯合子患者接受了心脏移植。我们的研究结果表明,NRAP的截断变异与外显率降低和临床变异性有关,这表明一种复杂的机制超越了简单的孟德尔遗传。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Reduced Penetrance and Variable Expression of Dilated Cardiomyopathy Associated With Homozygous Truncating Variants in NRAP Gene.

Dilated Cardiomyopathy (DCM) is a genetically heterogeneous condition of left ventricular dilation and systolic dysfunction, leading to heart failure. It is mostly inherited in a dominant pattern. Recessive inheritance has been rarely encountered. This study aims to outline the clinical and genetic characteristics associated with recessively inherited NRAP truncating variants in our highly consanguineous population. Twenty-three cases from 12 unrelated consanguineous families were recruited. Cardiological evaluation and genetic testing with exome sequencing (ES) were conducted in all cases, followed by segregation analysis of first-degree relatives. Genetic analysis with ES identified five unique homozygous truncating variants in NRAP in the affected cases. The segregation analysis detected a total of 23 homozygous and 21 heterozygous individuals. Out of the total homozygous cases, three were asymptomatic, while 20 exhibited symptoms with remarkable inter- and intrafamilial variability of the age of onset (range: 9 months to 47 years, median 10 years), seven of whom died (range: 9 months to 28 years, median 7 years). None of the heterozygous individuals showed symptoms. Of note, three homozygous cases underwent heart transplantation. Our findings show that truncating variants in NRAP are associated with reduced penetrance and clinical variability, suggesting a complex mechanism beyond simple Mendelian inheritance.

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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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