Audiological and genetic features of themtDNA mutations

Abstract

Conclusions Significant difference in the incidence of mitochondrial DNA (mtDNA) mutations was found between the Chinese and USA populations. The identification of the mtDNA A1555G mutation in a large proportion of Chinese probands with nonsyndromic sensorineural hearing loss (NSHL) provides a molecular explanation for the high prevalence of aminoglycoside-induced deafness in China. Objective The aim was to characterize the audiological and genetic features of NSHL due to mutations in mtDNA. Subjects and methods The mtDNA and audiogram analyses were performed in 498 NSHL patients (290 from China and 208 from the USA) with and without history of aminoglycoside exposure. A PCR and restriction enzyme digestion protocol was used for mutational screening and the European Workshop on Genetic Hearing Loss criteria were applied for audiological classification. Results All Chinese probands (15.5%) with mtDNA mutation were found to carry the homoplasmic mtDNA A1555G mutation, whereas four probands (1.9%) from the USA were found to carry the mtDNA A1555G and two (1%) had mtDNA G7444A. Approximately 63% of the probands with mtDNA mutations had post-lingual hearing loss and 56.8% of them had a medical history of exposure to aminoglycosides. Hearing losses are bilateral, sensorineural, and symmetric. The main audiogram shapes found were sloping.

Molecular epidemiological analysis of mitochondrial DNA12SrRNA A1555G,GJB2,andSLC26A4mutations in sporadic outpatients with nonsyndromic sensorineural hearing loss in China

“…For example, previous findings showed that the frequency was 2.9% in patients with NSHL [14]. Guo et al [3] reported that the frequency was 8.75% in NSHL patients in special education schools in northwest China, and 15.5% was reported by Liu et al [6], even up to 40% in 10 Taiwan families with deafness [17]. Noguchi et al [16] reported that the mutation frequency was higher in familial patients than in sporadic patients.…”

“…The differences were mainly found in mutation frequencies, including disease-causing mutation frequency (homozygous or compound heterozygous mutation), and risk allele carrying frequency (homozygous, compound heterozygous and heterozygous mutation). For example, the reported m.A1555G mutation frequency in Chinese NSHL patients varied from 1.67% to 15.5% in several independent studies [5,6]. The difference among reported mutation frequencies of GJB2 gene was very large.…”

The genetic bases for non-syndromic hearing loss among Chinese

“…111 Our data shows that 88% of severe-profound mt DNA deafness carrying the homoplasmic A1555G mutation had exposure to aminoglycosides. 112 …”

“…Our recent study shows that the mt DNA A1555G is responsible for deafness for a large proportion of NSHL, accounting for 15.5% of SNHL cases from the special clinics for deaf in China. 112 …”

Application of SNPscan in Genetic Screening for Common Hearing Loss Genes

“…Homoplasmic m.1555A > G and m.1494C > T, located at the highly conserved decoding site of the 12S ribosomal RNA gene, have been identified as a cause of maternally inherited non-syndromic HL. HL inherited through the mitochondria accounts for less than 1% of all HL, though the frequency of m.1555A > G in Chinese non-syndromic HL patients can vary from 1.67%-15.5% [17–20]. In this study, 5 cases (0.72%,5/695) were found to carry homoplasmic m.1555A > G, out of which, 1 had a history of aminoglycoside antibiotic usage and another had a recognizable audio-profile of aminoglycoside-induced HL.…”