Role of the Mitochondrial Mutations, m.827A>G and the Novel m.7462C>T, in the Origin of Hearing Loss

Abstract

Samples from 30 deaf probands exhibiting features suggestive of syndromic mitochondrial deafness or from families with maternal transmission of deafness were selected for investigation of mutations in the mitochondrial genes MT-RNR1 and MT-TS1. Patients with mutation m.1555A>G had been previously excluded from this sample. In the MT-RNR1 gene, five probands presented the m.827A>G sequence variant, of uncertain pathogenicity. This change was also detected in 66 subjects of an unaffected control sample of 306 Brazilian individuals from various ethnic backgrounds. Given its high frequency, we consider it unlikely to have a pathogenic role on hereditary deafness. As to the MT-TS1 gene, one proband presented the previously known pathogenic m.7472insC mutation and three probands presented a novel variant, m.7462C>T, which was absent from the same control sample of 306 individuals. Because of its absence in control samples and association with a family history of hearing impairment, we suggest it might be a novel pathogenic mutation.

Analysis of mitochondrial alterations in Brazilian patients with sensorineural hearing loss using MALDI-TOF mass spectrometry

“…A significant difference in the proportion of individuals with the A827G mutation among the patients with HL (13 %) and normal hearing controls (8.6 %) was observed. Similar results were found in other studies in different populations [ 30 – 32 ]. The A827G mutation has been implicated in aminoglycoside ototoxicity and nonsyndromic HL.…”

“…However, the incomplete penetrance indicates that the A827G mutation alone is not sufficient to produce clinical phenotype, requiring the involvement of modifying factors including aminoglycosides, mitochondrial haplotypes or nuclear modifier genes [ 34 – 36 ]. On the other hand, the contribution of this variant to HL remains controversial, given its high frequency in the normal population [ 32 ].…”

Genetic Epidemiology of Mitochondrial Pathogenic Variants Causing Nonsyndromic Hearing Loss in a Large Cohort of South Indian Hearing Impaired Individuals

“…This variant was observed in the homoplasmic state in two nonsyndromic sporadic subjects (AJ7 and AJ27). The frequency of m.7472insC varies from 0.5% to 3.3% in Caucasian, European, and American populations (Hutchin et al., ; Jacobs et al., ; Uehara et al., ). This variant was observed in 0.3% of the Japanese non syndromic hearing impaired population (Kato et al., 2012).…”

(Re) Conhecendo a USP: contribuições do ensino, da pesquisa e da extensão no campo das deficiências

“…O estudo do gene da pendrina foi alvo de projeto de mestrado (NONOSE, 2013). As mutações mitocondriais responsáveis por deficiência auditiva foram alvo de diversos projetos de iniciação científica e de mestrado das alunas Daniela Uehara, Juliana Carnavalli e Dayane Bernardino da Cruz, resultando também em publicações importantes (ABREU-SILVA, 2006a, 2006bUEHARA, 2010).…”