Abstract
Genetic factors are an important cause of idiopathic sensorineural hearing impairment (SNHI). From the epidemiological perspective, mutations of three deafness genes: GJB2, SLC26A4, and MT-RNR1, are much more prevalent than those of other genes worldwide. However, mutation spectra of common deafness genes differ remarkably across different populations. Here, we performed comprehensive genetic examination and haplotype analyses in 188 unrelated Mongolian families with idiopathic SNHI, and compared their mutation spectra and haplotypes to those of other European and Asian cohorts. We confirmed genetic diagnoses in 18 (9.6%) of the 188 families, including 13 with bi-allelic GJB2 mutations, three with bi-allelic SLC26A4 mutations, and two with homoplasmic MT-RNR1 m.1555A>G mutation. Moreover, mono-allelic mutations were identified in 17 families (9.0%), including 14 with mono-allelic GJB2 mutations and three with mono-allelic SLC26A4 mutations. Interestingly, three GJB2 mutations prevalent in other populations, including c.35delG in Caucasians, c.235delC in East Asians, and c.-23+1G>A in Southwest and South Asians, were simultaneously detected in Mongolian patients. Haplotype analyses further confirmed founder effects for each of the three mutations, indicating that each mutation derived from its ancestral origin independently. By demonstrating the unique spectra of deafness-associated mutations, our findings may have important clinical and scientific implications for refining the molecular diagnostics of SNHI in Mongolian patients, and for elucidating the genetic relationships among Eurasian populations.
Highlights
Hearing impairment is the most common inherited sensory defect
Three GJB2 mutations that are prevalent in other populations, including c.35delG in Caucasians [5,6,7], c.235delC in East Asians [10,11,12], and c.-23+1G>A in Southwest and South Asians [13,14,15,16], were simultaneously detected in Mongolian patients
This is the first study in the literature to identify these three common GJB2 mutations with significant allele frequencies in a single ethnic group
Summary
Hearing impairment is the most common inherited sensory defect. It is estimated that permanent sensorineural hearing impairment (SNHI) occurs in approximately 1.9 per 1000 live births [1], and with late-onset SNHI included, the disorder may affect 2% of school-age children [2, 3]. Among the plethora of HHI genes, mutations in three: GJB2 (MIM 121011), SLC26A4 (MIM 605646), and the mitochondrial 12S rRNA gene (MT-RNR1; MIM 561000), are prevalent in deaf patients across different populations [4]. Predominant mutations in these genes differ significantly across populations. Predominant SLC26A4 mutations differ among populations, including p.T416P and c.1001G>A in Caucasians [17, 18], p.H723R in Japanese [19] and Koreans [20], and c.919-2A>G in Han Taiwanese [21] and Han Chinese [22] These findings underscore the indispensability of collecting regional data when genetic examination for SNHI is performed in a specific population
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