Contribution of SLC26A4 to the molecular diagnosis of nonsyndromic prelingual sensorineural hearing loss in a Brazilian cohort

Simone da Costa e Silva Carvalho,Clarissa Gondim Picanço-Albuquerque,Wilson Araujo Silva,Thaís Oliveira dos Anjos,Carlos Henrique Paiva Grangeiro,Greice Andreotti De Molfetta,Victor Evangelista de Faria Ferraz

doi:10.1186/s13104-018-3647-4

Simone da Costa e Silva Carvalho, Clarissa Gondim Picanço-Albuquerque + Show 5 more

Open Access

https://doi.org/10.1186/s13104-018-3647-4

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Abstract

ObjectiveHereditary hearing loss (HL) is the most common sensorineural disorder in humans. Besides mutations in GJB2 and GJB6 genes, pathogenic variants in the SLC26A4 gene have been reported as a cause of hereditary HL due to its role in the physiology of the inner ear. In this research we wanted to investigate the prevalence of mutations in SLC26A4 in Brazilian patients with nonsyndromic prelingual sensorineural HL. We applied the high-resolution melting technique to screen 88 DNA samples from unrelated deaf individuals that were previously screened for GJB2, GJB6 and MT-RNR1 mutations.ResultsThe frequency of mutations in the SLC26A4 gene was 28.4%. Two novel mutations were found: p.Ile254Val and p.Asn382Lys. The mutation c.-66C>G (rs17154282) in the promoter region of SLC26A4, was the most frequent mutation found and was significantly associated with nonsyndromic prelingual sensorineural HL. After mutations in the GJB2, GJB6 and mitochondrial genes, SLC26A4 mutations are considered the next most common cause of hereditary HL in Brazilian as well as in other populations, which corroborates with our data. Furthermore, we suggest the inclusion of the SCL26A4 gene in the investigation of hereditary HL since there was an increase in the frequency of the mutations found, up to 22.7%.

Highlights

Sensorineural hearing loss (SNHL) is the most common sensorineural impairment in humans, and it is associated with abnormalities of inner ear structures
After mutations in the GJB2, GJB6 and mitochondrial genes, SLC26A4 mutations are considered the most common cause of heredi‐ tary HL in Brazilian as well as in other populations, which corroborates with our data
We suggest the inclusion of the SCL26A4 gene in the investigation of hereditary HL since there was an increase in the frequency of the mutations found, up to 22.7%

Summary

Results

In relation to the degree of hearing impairment, most individuals presented profound (55.7%) or severe (20.4%) hearing loss (HL). About 22.7% of the mutations were found in heterozygosity or compound heterozygosity and 5.7% in double heterozygosity with the GJB2 and GJB6 genes (Table 3) For three of those mutations, it was possible to screen the frequency in the control group of 96 healthy individuals. The most frequent mutation found was the c.-66C>G (rs17154282), located in the non-coding exon 1 of the SLC26A4 gene (NM_000441.1) and it was found in 14.8% of the cohort This mutation was significantly associated with nonsyndromic prelingual SNHL patients (OR = 0.33, 95% CI 0.09–1.05, p = 0.03684) when compared to the control group. The novel mutations p.Ile254Val and p.Asn382Lys were found, and this study constitutes the first report on both mutations in prelingual SNHL patients Both mutations were shown to be pathogenic by the in silico tools PolyPhen-2 and CADD, but we found no significant association of those mutations with SNHL (p = 0.3052) when we compared to the mutation frequency in the control group. No correlations were found between the clinical features and the genotypes

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