Deafness, Autosomal Dominant 20

A number sign (#) is used with this entry because this form of autosomal dominant progressive sensorineural hearing loss, DFNA20/26, is caused by heterozygous mutation in the gamma-actin gene (ACTG1; 102560) on chromosome 17q25.

Clinical Features

Morell et al. (2000) reported a 3-generation family living in the U.S. Midwest in which some members had a bilateral, sloping, progressive, sensorineural hearing loss, first evident at 6,000 and 8,000 Hz. It was identified in some family members in the early teens but was clearly evident by the early twenties. The degree of hearing loss increased with age, and threshold shifts were seen at all frequencies.

DeWan et al. (2003) described another U.S. family in which affected members had sloping audiograms with mid- and high-frequency hearing loss, which progressed to hearing loss that affected all frequencies. Mean age at onset of hearing impairment was 13.2 years, with a standard deviation of 4.6 years.

Rendtorff et al. (2006) provided follow-up of a large Norwegian family originally reported by Teig (1968) with autosomal dominant sensorineural hearing loss spanning 7 generations. Age at onset was in the first or second decade of life. Hearing loss first affected high frequencies and progressed to involve all frequencies. Audiograms showed a sloping configuration with age, resulting in profound hearing loss. The rate of progression was variable, but most affected members in this family needed a hearing aid by age 20 years.

Mapping

Using a genomewide screen, Morell et al. (2000) demonstrated linkage of the disorder, designated DFNA20, to chromosome 17q25. By haplotype analysis, they refined the DFNA20 critical region to 12 cM between D17S1806 and D17S668. Morell et al. (2000) noted that the mouse mutation jackson-shaker (js), which causes deafness and circling behavior, maps to a region of chromosome 11 that has homology with human 17q25.

Yang and Smith (2000) reported 2 unrelated American families with progressive autosomal dominant hearing loss that mapped to chromosome 17q25. They designated the locus DFNA26.

DeWan et al. (2003) found significant linkage to 17q25.3 (maximum 2-point lod score of 6.32) in a U.S. family with hearing loss. The authors concluded that DFNA20 and DFNA26 are probably the same or allelic disorders. They also noted that Usher syndrome type 1G (USH1G; 606943) maps to the same region and may be allelic.

Molecular Genetics

In affected members of 4 families with autosomal dominant progressive sensorineural hearing loss (DFNA20/DFNA26), Zhu et al. (2003) identified heterozygous mutations in highly conserved regions of the ACTG1 gene (102560.0001-102560.0004). Three of the families had been reported by Yang and Smith (2000) and DeWan et al. (2003). The findings established that DFNA20 and DFNA26 are identical.

In affected members of a Dutch family with autosomal dominant deafness linked to the 17q25 region, Van Wijk et al. (2003) identified a mutation in the ACTG1 gene (102560.0005).

In 19 affected individuals of a large Norwegian family reported by Teig (1968), Rendtorff et al. (2006) identified a heterozygous mutation in the ACTG1 gene (102560.0006).

Morin et al. (2009) reported 2 Spanish families with autosomal deafness and identified heterozygous mutations (102560.0007 and 102560.0008, respectively) in the ACTG1 gene.