Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase

Aviva Levitas, Emad Muhammad, Gali Harel, Ann Saada, Vered Chalifa Caspi, Esther Manor, John C. Beck, Val Sheffield, Ruti Parvari

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


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.

Original languageEnglish
Pages (from-to)1160-1165
Number of pages6
JournalEuropean Journal of Human Genetics
Issue number10
StatePublished - 1 Oct 2010


  • SDHA
  • mutation
  • neonatal isolated cardiomyopathy
  • recessive inheritance


Dive into the research topics of 'Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase'. Together they form a unique fingerprint.

Cite this