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.
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。