Mitochondrial non-syndromic sensorineural hearing loss: a clinical, audiological and pathological study from Italy, and revision of the literature

Abstract

Over the last decade, a number of distinct mutations in the mtDNA (mitochondrial DNA) have been found to be associated with both syndromic and non-syndromic forms of hearing impairment. Their real incidence as a cause of deafness is poorly understood and generally underestimated. Among the known mtDNA mutations, the A1555G mutation in the 12S gene has been identified to be one of the most common genetic cause of deafness, and it has been described to be both associated to non-syndromic progressive SNHL (sensorineural hearing loss) and to aminoglycoside-induced SNHL. In the present study, we have investigated the presence of mtDNA alterations in patients affected by idiopathic non-syndromic SNHL, both familiar and sporadic, in order to evaluate the frequency of mtDNA alterations as a cause of deafness and to describe the audiological manifestations of mitochondrial non-syndromic SNHL. In agreement with previous studies, we found the A1555G mutation to be responsible for a relevant percentage (5.4%) of cases affected with isolated idiopathic sensorineural hearing impairment.

Complete Mitochondrial Genome Analysis and Clinical Documentation of a Five-Generational Indian Family with Mitochondrial 1555A>G Mutation and Postlingual Hearing Loss

“…In another study by Silan et al (2011) among 64 Turkish prelingual hearing impaired subjects, one sporadic case was found to carry both a heterozygous c.35delG mutation in the GJB2 gene and the mitochondrial m.1555A>G mutation. GJB2 and GJB6 gene mutations were not present in any of the nine Italian idiopathic hearing loss subjects with the m.1555A>G mutation (Berrettini et al, 2008). No pathogenic mutations in the GJB2, GJB6 and SLC26A4 nuclear genes were observed along with the m.A1555G mutation in three unrelated idiopathic hearing loss subjects from the same region (Guaran et al, 2013).…”

“…In a large Japanese pedigree with postlingual hearing loss, Matsunaga et al (2005) described variable phenotypic expression of hearing loss without exposure to aminoglycoside antibiotics. Berrettini et al (2008) studied nine Italian familial idiopathic hearing impaired subjects with the m.1555A>G mutation. Three of the nine subjects had a history of aminoglycoside antibiotic exposure.…”

Hearing Loss in a Patient With the Myopathic Form of Mitochondrial DNA Depletion Syndrome and a Novel Mutation in the TK2 Gene

“…One of the pathogenic changes most frequently found in mtDNA, the A3243G mutation in the tRNA Leu(UUR) has been associated in some cases to diabetes plus deafness, although the same mutation was also reported in isolated deafness (17). Nonsyndromic hearing loss is a landmark in patients with the A1555G mutation in the 12S rRNA gene (18,19). In most patients harboring this mutation, hearing loss occurs after aminoglycoside treatment, but cases of deafness caused by A1555G without aminoglycoside exposure are not infrequent (19).…”

“…The patient did not show symptoms of noticeable hearing dysfunction before the age of 3 y, suggesting a progressive hearing loss to moderate deafness starting around this age. This progressive pattern is common in deafness due to mitochondrial dysfunction (18).…”

Analysis of a Large-Scale Screening of Mitochondrial DNA m.1555A>G Mutation in 2417 Deaf–Mute Students in Northwest of China

“…A number of racial populations over the world have been screened for the locus mtDNA m.1555A>G, again indicating markedly different mutation rates among different geographic or racial origins. In Caucasians living in Europe or America, the m.1555A>G mutation rates of sporadic patients are 0.6%-2.4% (Li et al, 2004;Berrettini et al, 2008;Konings et al, 2008;Rydzanicz et al, 2009); in Mongoloids living in East and Southeast Asia, a rate of 1.6%-8.56% was observed (Pandya et al, 1999;Oshima et al, 2001;Li et al, 2004;Guo et al, 2008;Wu et al, 2008), but it was not found among 122 and 221 nonsyndromic hearing loss subjects in Australia and North India, respectively (Ramsebner et al, 2007;Bhalla et al, 2009). Northwest China covers Shaanxi, Gansu, Qinghai, Ningxia, and Xinjiang.…”