Mitochondrial DNA Variation Dictates Expressivity and Progression of Nuclear DNA Mutations Causing Cardiomyopathy.

ABSTRACT: Nuclear-encoded mutations causing metabolic and degenerative diseases have highly variable expressivity. Patients sharing the homozygous mutation (c.523delC) in the adenine nucleotide translocator 1 gene (SLC25A4, ANT1) develop cardiomyopathy that varies from slowly progressive to fulminant. This variability correlates with the mitochondrial DNA (mtDNA) lineage. To confirm that mtDNA variants can modulate the expressivity of nuclear DNA (nDNA)-encoded diseases, we combined in mice the nDNA Slc25a4^-/- null mutation with a homoplasmic mtDNA ND6^P25L or COI^V421A variant. The ND6^P25L variant significantly increased the severity of cardiomyopathy while the COI^V421A variant was phenotypically neutral. The adverse Slc25a4^-/- and ND6

SUBMITTER: McManus MJ 

PROVIDER: S-EPMC6717513 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature