Loss of function variants in human PNPLA8 encoding calcium-independent phospholipase A2 γ recapitulate the mitochondriopathy of the homologous null mouse.

ABSTRACT: Mitochondriopathies are a group of clinically heterogeneous genetic diseases caused by defects in mitochondrial metabolism, bioenergetic efficiency, and/or signaling functions. The large majority of proteins involved in mitochondrial function are encoded by nuclear genes, with many yet to be associated with human disease. We performed exome sequencing on a young girl with a suspected mitochondrial myopathy that manifested as progressive muscle weakness, hypotonia, seizures, poor weight gain, and lactic acidosis. She was compound heterozygous for two frameshift mutations, p.Asn112HisfsX29 and p.Leu659AlafsX4, in the PNPLA8 gene, which encodes mitochondrial calcium-independent phospholipase A2 γ (iPLA2 γ). Western blot analysis of affected muscle displayed the absence of PNPLA8 protein. iPLA

SUBMITTER: Saunders CJ 

PROVIDER: S-EPMC4361307 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature