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Phenotypic spectrum of ALPK3 ‐related cardiomyopathy
Author(s) -
Al Senaidi Khalfan,
Joshi Niranjan,
AlNabhani Maryam,
AlKasbi Ghalia,
Al Farqani Abdullah,
AlThihli Khalid,
AlMaawali Almundher
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61176
Subject(s) - cardiomyopathy , hypertrophic cardiomyopathy , medicine , phenotype , dilated cardiomyopathy , etiology , cohort , cardiology , restrictive cardiomyopathy , heart failure , genetics , biology , gene
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.639G>A: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.