Co-occurrence of m.15992A>G and m.15077G>A Is Associated With a High Penetrance of Maternally Inherited Hypertension in a Chinese Pedigree

Abstract

Abstract BACKGROUND Mitochondrial DNA (mtDNA) pathogenic variants have been identified to be associated with maternally inherited essential hypertension (MIEH). However, the distinctive clinical features and molecular pathogenesis of MIEH are not fully understood. METHODS In this study, we collected a Chinese MIEH family with extraordinary higher penetrance of essential hypertension (88.89%) and early ages of onset (31–40 years old), and performed clinical and genetic characterization for this family. The complete mitochondrial genome of the proband was sequenced and analyzed. RESULTS The maternally related members in this family were presented with severe increased blood pressure, left ventricular remodeling, and metabolic abnormalities. Through sequencing the entire mtDNA of the proband and performing systematic analysis of the mtDNA variants with a phylogenic approach, we identified a potentially pathogenic tRNA variant (m.15992A>G in the MT-TP gene) that may account for the MIEH in this family. One nonsynonymous variant (m.15077G>A in the MT-CYB gene) was identified to play a synergistic role with m.15992A>G to cause a high penetrance of MIEH. CONCLUSIONS Our results, together with previous findings, have indicated that tRNA pathogenic variants in the mtDNA could act important roles in the pathogenesis of MIEH through reducing mitochondrial translation and disturbing mitochondrial function.