Sudden Cardiac Death Due to Deficiency of the Mitochondrial Inorganic Pyrophosphatase PPA2.

ABSTRACT: We have used whole-exome sequencing in ten individuals from four unrelated pedigrees to identify biallelic missense mutations in the nuclear-encoded mitochondrial inorganic pyrophosphatase (PPA2) that are associated with mitochondrial disease. These individuals show a range of severity, indicating that PPA2 mutations may cause a spectrum of mitochondrial disease phenotypes. Severe symptoms include seizures, lactic acidosis, cardiac arrhythmia, and death within days of birth. In the index family, presentation was milder and manifested as cardiac fibrosis and an exquisite sensitivity to alcohol, leading to sudden arrhythmic cardiac death in the second decade of life. Comparison of normal and mutant PPA2-containing mitochondria from fibroblasts showed that the activity of inorganic pyrophosph

SUBMITTER: Kennedy H 

PROVIDER: S-EPMC5011043 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature