%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.