Phenotypic spectrum of ALPK3 ALPK3 ‐related cardiomyopathy

摘要

Abstract Cardiomyopathies are clinically heterogeneous disorders and are the leading cause of cardiovascular morbidity and mortality. Different etiologies have a significant impact on prognosis. Recently, novel biallelic loss‐of‐function pathogenic variants in alpha‐kinase 3 ( ALPK3 ) were implicated in causing early‐onset pediatric cardiomyopathy (cardiomyopathy, familial hypertrophic 27; OMIM 618052). To date, eight patients, all presented during early childhood, were reported with biallelic ALPK3 pathogenic variants. We describe the molecular and clinical phenotype characterization of familial cardiomyopathy on one family with six affected individuals. We identified homozygosity for an ALPK3 deleterious sequence variant (NM_020778.4:c.639GA:p.Trp213*) in all the affected individuals. They presented with either dilated cardiomyopathy that progressed to hypertrophic cardiomyopathy (HCM) or HCM with left ventricular noncompaction. The age of presentation in our cohort extends between infancy to the fourth decade. The phenotypic severity decreases with the progression of age.