%0 Case Reports
%T Molecular 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.
%A Kraoua L
%A Jaouadi H
%A Allouche M
%A Achour A
%A Kaouther H
%A Ahmed HB
%A Chaker L
%A Maazoul F
%A Ouarda F
%A Zaffran S
%A M'rad R
%J Mol Genet Genomic Med
%V 10
%N 7
%D 07 2022
%M 35656879
%F 2.473
%R 10.1002/mgg3.1954
%X 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.