Abstract：
Genetic cardiac diseases are the main trigger of sudden cardiac death (SCD) in young adults. Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiomyopathy and accounts for 0.5 to 1% of SCD cases per year.
Herein, we report a family with a marked history of SCD focusing on one SCD young adult case and one pediatric case with HCM.
For the deceased young adult, postmortem whole-exome sequencing (WES) revealed a missense variant in the ACTN2 gene: c.355G > A; p.(Ala119Thr) confirming the mixed hypertrophic/dilated cardiomyopathy phenotype detected in the autopsy. For the pediatric case, WES allowed us the identification of a novel frameshift variant in the LZTR1 gene: c.1745delT; p.(Val582Glyfs*10) which confirms a clinical suspicion of HCM related to Noonan syndrome.
The present study adds further evidence on the pathogenicity of ACTN2: p. Ala119Thr variant in SCD and expands the mutational spectrum of the LZTR1 gene related to Noonan syndrome.
Herein, we report a family with a marked history of SCD focusing on one SCD young adult case and one pediatric case with HCM.
For the deceased young adult, postmortem whole-exome sequencing (WES) revealed a missense variant in the ACTN2 gene: c.355G > A; p.(Ala119Thr) confirming the mixed hypertrophic/dilated cardiomyopathy phenotype detected in the autopsy. For the pediatric case, WES allowed us the identification of a novel frameshift variant in the LZTR1 gene: c.1745delT; p.(Val582Glyfs*10) which confirms a clinical suspicion of HCM related to Noonan syndrome.
The present study adds further evidence on the pathogenicity of ACTN2: p. Ala119Thr variant in SCD and expands the mutational spectrum of the LZTR1 gene related to Noonan syndrome.
摘要：
遗传性心脏病是年轻人心源性猝死（SCD）的主要诱因。肥厚型心肌病（HCM）是最常见的心肌病，每年占SCD病例的0.5％至1％。
这里，我们报告了一个有明显SCD病史的家庭,重点是1例SCD年轻成人病例和1例HCM儿科病例.
对于死去的年轻人，验尸全外显子组测序（WES）揭示了ACTN2基因中的错义变异：c.355G>A;p。（Ala119Thr）证实了尸检中检测到的混合肥大/扩张型心肌病表型。对于儿科病例，WES使我们能够鉴定LZTR1基因中的新型移码变体：c.1745delT；p。（Val582Glyfs*10），这证实了临床怀疑与Noonan综合征有关的HCM。
本研究为ACTN2的致病性增加了进一步的证据：p。Ala119Thr变异体在SCD中的致病性，并扩展了与Noonan综合征相关的LZTR1基因的突变谱。
这里，我们报告了一个有明显SCD病史的家庭,重点是1例SCD年轻成人病例和1例HCM儿科病例.
对于死去的年轻人，验尸全外显子组测序（WES）揭示了ACTN2基因中的错义变异：c.355G>A;p。（Ala119Thr）证实了尸检中检测到的混合肥大/扩张型心肌病表型。对于儿科病例，WES使我们能够鉴定LZTR1基因中的新型移码变体：c.1745delT；p。（Val582Glyfs*10），这证实了临床怀疑与Noonan综合征有关的HCM。
本研究为ACTN2的致病性增加了进一步的证据：p。Ala119Thr变异体在SCD中的致病性，并扩展了与Noonan综合征相关的LZTR1基因的突变谱。
