Deafness, Autosomal Dominant 23

A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-23 (DFNA23) is caused by heterozygous mutation in the SIX1 gene (605192) on chromosome 14q23.

Clinical Features

Salam et al. (2000) studied DNA samples from 22 members of a Swiss-German kindred in 3 generations: 10 with hearing impairment, 8 unaffected, and 4 spouses of hearing-impaired pedigree members. The hearing-impaired family members had prelingual bilateral symmetric hearing loss. All audiograms from the hearing-impaired individuals displayed sloping curves, with hearing ability ranging from normal hearing to mild hearing loss in low frequencies, normal hearing to profound hearing loss in mid-frequencies, and moderate to profound hearing loss in high frequencies. A conductive component existed for 50% of the hearing-impaired family members. Most of the hearing-impaired family members did not display progression of hearing loss.

Ali Mosrati et al. (2011) reported a Tunisian family (KH) with bilateral moderate to profound hearing impairment. Hearing loss was both mixed and sensorineural, and some individuals had bilateral or unilateral preauricular pits. No other anomalies, such as branchial arch remnants, were observed. Temporal bone computed tomography in 3 affected individuals showed no inner ear malformations. No kidney malformations were found on renal ultrasound of the patients.

Mapping

By linkage analysis, Salam et al. (2000) mapped the deafness locus (DFNA23) in this family to 14q21-q22, with a maximum multipoint lod score of 5.1 at marker D14S290.

Molecular Genetics

In an affected member of the family reported by Salam et al. (2000), Ruf et al. (2004) identified a mutation in the SIX1 gene (601205.0003). The patient was also found to have a solitary left hypodysplastic kidney with vesicoureteral reflux and progressive renal failure, suggesting that this family may have BOR/BO syndrome (see 608389).

In affected members of a Tunisian family with autosomal dominant nonsyndromic hearing impairment showing linkage to 14q23, Ali Mosrati et al. (2011) identified a heterozygous missense mutation in the SIX1 gene (601205.0005). The mutation segregated with the phenotype in the family.