G and m.3243A>G show distinct differences

Abstract

Background: Hearing loss is one of the most common symptoms of mitochondrial disorders. However, audiological pheno-types associated with different molecular defects in mtDNA are not yet well characterized.Material/Methods: A large cohort of 1499 nonconsanguineous patients aged 5-40 years with hearing loss of unknown etiology was screened for mutations in mtDNA. For further analysis, patients harboring m.1555A>G and m.3243A>Gwere selected. Hearing status of the patients was assessed by pure tone audiometry. Patterns of audiograms (hearing thresh-old levels at each examined frequency) were statistically compared among the carriers of the m.1555A>G and the m.3243A>G mutations. Results: We identified 20 patients positive for m.1555A>G mutation and 16 patients positive for m.3243A>G change. The frequency of the above transitions was calculated in our cohort as 1.33% and 1.06%, respectively. Seventeen affected family members carrying the mutations were included into the study. Typical shape of the audiograms in patients with m.1555A>G mutation presented a ski-slope pattern, whereas the audiometric curves among the m.3243A>G individuals had a pantonal shape (a flat curve) with slight downward sloping at the higher frequencies. The differences were statistically significant. The onset of hearing loss was noted earlier among m.1555A>G than m.3243A>G patients (12.5 and 26 years, respectively). Aminoglycoside administration was declared in both groups in 11 and 4 cases respectively, and caused abrupt hearing deterioration in all cases. Conclusions: A pattern of audiogram in patients with mitochondrial deafness may suggest a localization of mtDNA mutation. The pathogenesis of the audiometric differences needs further study.