ESPE Abstracts

A Chinese family of Han with symptoms of matrilineally-inherited obesity was assessed and its clinical, genetic, and molecular profiling was conducted. Obesity was observed in matrilineal relatives (3 out of 14) of a single generation (of 3 alive generations) of this family. On pedigree analysis and sequencing of their mitochondrial DNA, a novel homoplasmic mutation of the mitochondrial tRNA^Thr gene (15894G>A) was identified in these individuals. This mutation correlated with a destabilized conserved base pair in this tRNA acceptor stem. Position 7 is known to be crucial for carrying out effective codon recognition and stability of tRNA. In accordance with the importance of this conserved site, we observed that the predicted structure of this tRNA with the mutation was noticeably remodeled in a molecular dynamics simulation when compared to the isoform of the wild-type. All other mutations observed in the individual’s mtDNA were known variants belonging to Asian M7b haplogroup. Thus, this is the first report that provides evidence of the association between a mutation in tRNA and an enhanced risk of maternally-transmissible obesity, offering more insights into obesity and its underlying nature.