Audiologic and Genetic Features of the A3243G mtDNA Mutation

Abstract

Background: Mitochondrial mutations have been shown to be responsible for syndromic and nonsyndromic hearing impairment. Aim: To assess the genotypic-phenotypic correlation of mitochondrial DNA mutations in three generations of a single family. Methods: A single family with maternally inherited diabetes and hearing loss was recruited. Genomic DNA was subject to polymerase chain reaction-restriction fragment length polymorphism analysis (ApaI) for A3243G mutation detection and confirmation with direct DNA sequencing. The degree of heteroplasmy for the A3243G mutation in blood DNA samples was quantified. In addition, we reviewed audiological data of A3243G-associated hearing loss cases from the literature to provide details of audiologic features. Results: Six of 11 family members were recruited. All affected members harbored the A3243G mutation. Four of six members had diabetes. Five of five affected members demonstrated hearing loss ranging from mild to severe. The degree of heteroplasmy ranged from 5.51% to 27.74%. Conclusions: Patients with a greater percentage of heteroplasmy have a trend toward more severe phenotypic presentations. Hearing loss is bilateral, sensorineural, and symmetric. The main audiogram shapes found were sloping. Additional studies are necessary to clarify the relationship between degree of heteroplasmy and phenotypic presentation.

Effect of Diabetes Mellitus on Hearing

“…The association is so strong with m.3243A>G thought to account for up to 1% of diabetes and 0.3% of deafness. 7 Sensorineural hearing loss accounts for about 90% of all hearing loss. It is found in 23% of the population older than 65 years of age.…”

Lack of Association of Mitochondrial tRNA(Leu) A3243G Mutation with Allergic Chronic Rhinosinusitis Pathogenesis in South Indian Population

“…The PCR product was subjected for RFLP using restriction enzyme ApaI (Fermentas, United Kingdom). The presence of mtDNA A3243G mutation leads to the cleavage of the 161 bp PCR product into two fragments of sizes 87 bp and 74 bp respectively [11]. The restriction digest products were analyzed through 2-3% agarose gel electrophoresis containing ethidium bromide and visualized under ultraviolet light.…”