ISSN: ISSN: 2157-7412
+44 1223 790975
Cincinnati Children's Hospital Medical Center, USA
Posters & Accepted Abstracts: J Genet Syndr Gene Ther
Advances in next generation sequencing technology have resulted in a rapid increase in the molecular characterization of mitochondrial disease. Recent years, our laboratory has successfully used whole-exome sequencing to identify many novel disease causing genes associated with mitochondrial disease. The mitochondrial asparaginyl-tRNAsynthetase (NARS2) mutations cause Leigh syndrome and nonsyndromic hearing loss (DFNB94). We found that some mutation can disrupt dimerization of NARS2 and decrease steady-state levels of mt-tRNAAsn without aminoacylation defects. The cells with NARS2 mutations also display impaired oxygen consumption rate and OXPHOS deficiency that can be rescued by overexpression of wild type NARS2. Recently, we found that recessive SLC25A46 mutations cause optic nerve atrophyand axonal peripheral neuropathy. SLC25A46, putative mitochondrial carrier gene, is human homologs of Ugo1p. Furthermore, we demonstrate the SLC25A46 role in mediating mitochondrial morphology in vitro and in vivo. In zebrafish we found that loss-of-function affects the development and maintenance of neuronal processes and causes abnormal mitochondrial fusion morphology. Our result show many disease causing genes associated with mitochondrial disease are yet to be identified and whole-exome sequencing is very cost-effective for this process.