{Reference Type}: Case Reports
{Title}: 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.
{Author}: Kraoua L;Jaouadi H;Allouche M;Achour A;Kaouther H;Ahmed HB;Chaker L;Maazoul F;Ouarda F;Zaffran S;M'rad R;
{Journal}: Mol Genet Genomic Med
{Volume}: 10
{Issue}: 7
{Year}: 07 2022
{Factor}: 2.473
{DOI}: 10.1002/mgg3.1954
{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.<BR>Herein, we report a family with a marked history of SCD focusing on one SCD young adult case and one pediatric case with HCM.<BR>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.<BR>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.