ESPE Abstracts

In this study, we conducted a clinical, genetic, and molecular profiling of a Han Chinese family with evident of matrilineally-inherited obesity. Obesity was evident in 2/6 matrilineal relatives in a single generation of this family (of 3 available generations). When the mitochondrial DNA of these individuals was sequences and a pedigree analysis was performed, we were able to identify a novel homoplasmic mutation of the mitochondrial tRNA^Gly gene (10029A>G) in these individuals. This mutation was linked to destabilization of a conserved base pair in the anticodon of this tRNA. This position (position 43) is known to be important for mediating effective codon recognition and tRNA stability. Consistent with the importance of this conserved site, we found that the predicted structure of a tRNA^Gly structure bearing a 10029A>G mutation was markedly altered in a molecular dynamics simulation relative to the wild-type isoform. All other mutations identified in the mtDNA of these individuals (3 in total) were known variants associated with Asian haplogroup D4. As such, our report provides novel evidence of a link between a tRNA mutation and an elevated risk of maternally-transmissible obesity risk, offering potentially novel insights into the underlying nature of obesity.