title: Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase.
abstract: Cardiomyopathies are common disorders resulting in heart failure; the most frequent form is dilated cardiomyopathy (DCM), which is characterized by dilatation of the left or both ventricles and impaired systolic function. DCM causes considerable morbidity and mortality, and is one of the major causes of sudden cardiac death. Although about one-third of patients are reported to have a genetic form of DCM, reported mutations explain only a minority of familial DCM. Moreover, the recessive neonatal isolated form of DCM has rarely been associated with a mutation. In this study, we present the association of a mutation in the SDHA gene with recessive neonatal isolated DCM in 15 patients of two large consanguineous Bedouin families. The cardiomyopathy is presumably caused by the significant tissue-specific reduction in SDH enzymatic activity in the heart muscle, whereas substantial activity is retained in the skeletal muscle and lymphoblastoid cells. Notably, the same mutation was previously reported to cause a multisystemic failure leading to neonatal death and Leigh's syndrome. This study contributes to the molecular characterization of a severe form of neonatal cardiomyopathy and highlights extreme phenotypic variability resulting from a specific missense mutation in a nuclear gene encoding a protein of the mitochondrial respiratory chain.
authors.affiliation: Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Aviva
authors.initials: A
authors.lastname: Levitas
authors.forename: Emad
authors.initials: E
authors.lastname: Muhammad
authors.forename: Gali
authors.initials: G
authors.lastname: Harel
authors.forename: Ann
authors.initials: A
authors.lastname: Saada
authors.forename: Vered Chalifa
authors.initials: VC
authors.lastname: Caspi
authors.forename: Esther
authors.initials: E
authors.lastname: Manor
authors.forename: John C
authors.initials: JC
authors.lastname: Beck
authors.forename: Val
authors.initials: V
authors.lastname: Sheffield
authors.forename: Ruti
authors.initials: R
authors.lastname: Parvari
mesh_terms: D018912:Arabs / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D042963:Electron Transport Complex II / Q000235:genetics* / Q000378:metabolism; D005190:Family; D005260:Female; D005420:Flavoproteins / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D021122:Protein Subunits / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics
chemical_list: D005420:Flavoproteins; D021122:Protein Subunits; D042963:Electron Transport Complex II; C511268:SDHA protein, human; D013385:Succinate Dehydrogenase