SLC26A4 mutations in patients with moderate to severe hearing loss

Abstract

Mutations in SLC26A4 cause either syndromic or nonsyndromic hearing loss. We identified a link between hearing loss and DFNB4 in 3 of the 50 families participating in this study. Sequencing analysis revealed two SLC26A4 mutations, p.V239D and p.S57X, in affected members of the 3 families. These mutations have been previously reported in deaf individuals from the subcontinent, all of whom manifested profound deafness. The patients investigated in our study exhibited moderate to severe hearing loss. Our results show that inactivating SLC26A4 mutations that cause profound deafness can also be involved in the etiology of moderate to severe hearing loss. The type of mutation cannot predict the severity of the hearing loss in all cases, and there may be additional epistatic interactions that could modify the phenotype.

Fig. 1

Pedigrees of families HLRB2 (top), HLRB7 (center), and HLRB10 (bottom) with phenotype data and genotypes of microsatellite markers flanking SLC26A4. Solid circles (females) and squares (males) denote affected individuals. Haplotypes associated with deafness are shaded gray

Fig. 2

Pure tone audiograms for three children of family HLRB2 (top), two children of family HLRB7 (center), and three children of family HLRB10 (bottom). All affected individuals (identified by codes in Fig. 1) have moderate to severe hearing loss. Hearing thresholds are depicted for the left ear (solid lines) and the right ear (dotted lines)

Fig. 3

Representative sequence electropherograms of the mutations p.V239D (top) and p.S57X (bottom). Arrows indicate mutation sites. The normal and mutated codons are underlined in the respective traces (Color figure online)