RESUMEN
BACKGROUND/OBJECTIVE: The genetic landscape of sensorineural hearing impairment (SNHI) varies across populations. In Mongolia, previous studies have shown a lower prevalence of GJB2 mutations and a higher frequency of variants in other deafness-related genes. This study aimed to investigate the genetic variants associated with idiopathic SNHI in Mongolian patients. METHODS: We utilized the next-generation sequencing for investigating the causative mutations in 99 Mongolian patients with SNHI. RESULTS: We identified pathogenic variants in 53 of the 99 SNHI patients (54%), with SLC26A4 being the most frequently mutated gene. The c.919-2A>G variant in SLC26A4 was the most prevalent, accounting for 46.2% of the mutant alleles. In addition, we identified 19 other known and 21 novel mutations in a total of 21 SNHI genes in autosomal recessive or dominant inheritance patterns. CONCLUSIONS: Our findings expand the understanding of the genetic landscape of SNHI in Mongolia and highlight the importance of considering population-specific variations in genetic testing and counseling for SNHI.
Asunto(s)
Pérdida Auditiva Sensorineural , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Transportadores de Sulfato , Humanos , Mongolia/epidemiología , Masculino , Femenino , Pérdida Auditiva Sensorineural/genética , Transportadores de Sulfato/genética , Conexina 26/genética , Adulto , Niño , Adolescente , Preescolar , Adulto Joven , Persona de Mediana EdadRESUMEN
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.