Deafness, Autosomal Dominant 11

A number sign (#) is used with this entry because autosomal dominant deafness-11 (DFNA11) is caused by heterozygous mutation in the gene encoding myosin VIIA (MYO7A; 276903) on chromosome 11q13.

Autosomal recessive nonsyndromic deafness (DFNB2; 600060) and Usher syndrome type IB (276900) are allelic disorders.

Description

Autosomal dominant deafness-11 is a nonsyndromic form of progressive neurosensory hearing loss with postlingual onset. Some affected individuals have mild vestibular symptoms (summary by Sun et al., 2011).

Clinical Features

Tamagawa et al. (1996) reported a Japanese family with autosomal dominant nonsyndromic hearing loss. Most affected individuals noticed hearing loss in their first decade of life, after complete speech acquisition, with subsequent gradual progression. All affected individuals had bilateral sensorineural hearing loss without vertigo or associated symptoms. They had symmetric gently sloping or flat audiograms with hearing loss at all frequencies. Most affected individuals between the age of 20 and 60 years had moderate hearing loss.

Sun et al. (2011) reported 2 large unrelated Chinese families with autosomal dominant inheritance of postlingual nonsyndromic hearing loss. In 1 family, affected individuals had onset between ages 20 and 47 years of bilateral mild to severe symmetric hearing impairment particularly involving high frequencies. The audiogram was flat or downward sloping. Affected individuals in a second Chinese family had onset between ages 10 and 39 years of bilateral mild to severe symmetric hearing loss affecting mainly low frequencies. The audiogram was flat or ascending. In both families, high-frequency tinnitus occurred at the onset of hearing loss, but there was no vestibular involvement. Electrocochleography in the second family showed no evidence of endolymphatic hydrops.

Mapping

By linkage and haplotype analysis of a Japanese family with autosomal dominant nonsyndromic hearing loss, Tamagawa et al. (1996) found linkage to a locus, termed DFNA11, on chromosome 11q12.3-q21 between D11S1335 and D11S931. The authors noted that another locus for autosomal recessive nonsyndromic hearing loss, DFNB2 (600060), maps within the 11q12.3-q21 region at 11q13.5. Tamagawa et al. (1996) postulated that DFNB2 may be responsible for both recessive and dominant forms of deafness, or alternatively that several genes responsible for deafness map to the 11q12.3-q21 region. In the family reported by Tamagawa et al. (1996), lod scores of 3.25 at theta = 0 were observed for 5 markers, D11S527, D11S937, D11S918, D11S987, and D11S1314. Some of the alleles segregating with DFNA11 in this family were present in very low frequencies in the normal control population living in the same area.

In a review of nonsyndromic hearing impairment, Van Camp et al. (1997) referred to an unpublished family showing linkage of prelingual stable deafness to 11q22-q24. They referred to this autosomal dominant form as DFNA12 (601543).

Molecular Genetics

In affected members of the Japanese family with autosomal dominant nonsyndromic hearing loss mapping to 11q (Tamagawa et al., 1996), Liu et al. (1997) identified an in-frame 9-bp deletion in exon 22 of the MYO7A gene (276903.0011). The affected family members suffered from postlingual, bilateral, nonsyndromic sensorineural hearing loss, with gradual progression at all frequencies and minor vestibular problems. No evidence was found for retinitis pigmentosa (Tamagawa et al., 2002). Luijendijk et al. (2004) reported a similar family, from Holland, in which affected members were heterozygous for an asn458-to-ile mutation in the MY07A gene (N458I; 276903.0015).

Sun et al. (2011) reported 2 Chinese families with autosomal dominant deafness in whom they identified different heterozygous mutations in the MYO7A gene (D218N, 276903.0019 and G671S, 276903.0020, respectively).