TY - JOUR
T1 - Phenotypic spectrum of ALPK3-related cardiomyopathy
AU - Al Senaidi, Khalfan
AU - Joshi, Niranjan
AU - Al-Nabhani, Maryam
AU - Al-Kasbi, Ghalia
AU - Al Farqani, Abdullah
AU - Al-Thihli, Khalid
AU - Al-Maawali, Almundher
N1 - Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
KW - ALPK3
KW - cardiomyopathy
KW - dilated
KW - hypertrophic
UR - http://www.scopus.com/inward/record.url?scp=85065673707&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065673707&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.61176
DO - 10.1002/ajmg.a.61176
M3 - Article
C2 - 31074094
AN - SCOPUS:85065673707
SN - 1552-4825
VL - 179
SP - 1235
EP - 1240
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 7
ER -