ClinVar

In affected members of a family with maternally inherited nonsyndromic mild sensorineural deafness (500008), Leveque et al. (2007) identified a homoplasmic 3388C-A transversion in the MTDN1 gene, which was identified by whole mitochondrial genome analysis. The variant was predicted to not be pathogenic. Affected individuals had congenital to early adult onset of mild hearing loss associated with tinnitus and benign paroxysmal positional vertigo. Gutierrez Cortes et al. (2012) noted that the 3388C-A variant results in a leu28-to-met (L28M) substitution in a tyrosine-binding motif and a tyrosine kinase/phosphatase motif of the MTND1 protein. Cybrid cell lines carrying the mutation showed a 25% decline in mitochondrial oxygen consumption and a decrease of 55% in complex I activity compared to controls, indicating a defect in mitochondrial respiration. Complex I assembly, as assessed by gel electrophoresis, was also decreased (43% compared to controls), whereas other complexes were not affected. Reduced penetrance was observed.