Auditory Findings in Patients with Maternally Inherited Diabetes and Deafness Harboring a Point Mutation in the Mitochondrial Transfer RNA^{Leu (UUR)} Gene

Abstract

Five patients with sensorineural hearing loss, who harbored a point mutation in the mitochondrial transfer RNA (tRNA) gene tRNA(Leu) (UUR), from five unrelated family pedigrees were examined. In these families diabetes and deafness were maternally inherited. Bilateral hearing was more severely impaired at higher frequencies. Audiometric test results revealed that hearing loss involved the cochlea. Hearing gradually deteriorated; the progression rate ranged from 1.5 to 7.9 dB per year. Proportion of mutant mitochondrial DNAs (mtDNAs) in the leukocytes was not related to the rate or degree of hearing loss, although hearing loss appeared at a younger age in patients with higher heteroplasmy. We speculate that after the proportion of damaged mtDNAs, mostly as a result of mutation, exceeds the expression threshold for deficiencies in mitochondrial protein synthesis and oxygen consumption, a drop in adenosine triphosphate level could lead to an imbalance of ion concentration, resulting in cell death in the cochlea.

Frequency and clinical features of patients with sensorineural hearing loss associated with the A3243G mutation of the mitochondrial DNA in otorhinolaryngic clinics

“…In addition, SNHL in Japanese patients in otorhinolaryngic clinics previously reported to be due to the A3243G mutation was associated with DM (Oshima et al 1996;Tamagawa et al 1997;Usami et al 2000;Yamasoba et al 1996). The present results showed that all four patients with the mutation had family histories of maternal inheritance of SNHL, and three of the four cases were also associated with DM.…”

“…Therefore, it is apparent that a family history of possible Presented with SNHL and subsequently diagnosed as having glucose intolerance maternal inheritance of SNHL and association with DM are possible signs of the A3243G mutation in otorhinolaryngic clinics as well as in diabetes clinics. However, in a few cases in those previous reports, the onset of SNHL preceded that of DM (Tamagawa et al 1997;Yamasoba et al 1996), raising the possibility that these patients might have visited an otorhinolaryngic clinic before the presentation of DM. In addition, we herein report a case unassociated with DM (case 1).…”

“…Previous reports on 12 Japanese patients with SNHL due to the A3243G mutation but without MELAS showed that 10 patients showed the onset of hearing impairment between their twenties and their forties, and 1 patient, who also had chronic otitis media, experienced the onset of hearing loss at the age of 18, and 1 patient experienced the onset of SNHL at the age of 55 following the onset of DM at the age of 46 (Oshima et al 1996;Tamagawa et al 1997;Yamasoba et al 1996). Thus, the present study, together with the previous reports, suggests that an age of onset of hearing impairment between the teens and the forties is a sign suggesting the A3243G mutation.…”

The effects of coenzyme Q 10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation

“…Hearing loss was assessed by pure-tone audiometry. The pure tone average was calculated as the average of 0.5, 1, 2 and 4 kHz as described by Yamasoba [19]. The serum levels of CoQ 10 were determined by high-performance liquid chromatography [20].…”

The level of the mitochondrial mutation A3243G decreases upon ageing in epithelial cells from individuals with diabetes and deafness

“…The sensorineural hearing loss is bilateral, symmetric and originates in the cochlea. 5 This disorder is caused by an A-to-G transition at position 3243 of the mtDNA. The mutation is located in the gene encoding tRNA Leu , and results in impaired protein synthesis and electron transport chain dysfunction.…”