Open AccessMolecular autopsy and clinical family screening in a case of sudden cardiac death reveals ACTN2 mutation related to hypertrophic/dilated cardiomyopathy and a novel LZTR1 variant associated with Noonan syndrome
Author(s) -
Kraoua Lilia,
Jaouadi Hager,
Allouche Mohamed,
Achour Ahlem,
Kaouther Hakim,
Ahmed Habib Ben,
Chaker Lilia,
Maazoul Faouzi,
Ouarda Fatma,
Zaffran Stéphane,
M'rad Ridha
Publication year - 2022
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1954
Subject(s) - hypertrophic cardiomyopathy , medicine , missense mutation , sudden cardiac death , noonan syndrome , cardiomyopathy , dilated cardiomyopathy , exome sequencing , sudden death , autopsy , frameshift mutation , gene mutation , cardiology , mutation , pediatrics , genetics , gene , heart failure , biology
Background 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. Methods Herein, we report a family with a marked history of SCD focusing on one SCD young adult case and one pediatric case with HCM. Results 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. Conclusion 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.