Audiologic Aspects of the Search for DFNA20: A Gene Causing Late-Onset, Progressive, Sensorineural Hearing Loss

Abstract

The hearing loss demonstrated by this mid-Michigan family is a novel form of nonsyndromic, genetic, late-onset, bilateral, progressive, sensorineural hearing loss. The locus of the gene, the 20th for autosomal dominant hearing loss, is at band 17q25 of chromosome 17.

Actin in hair cells and hearing loss

“…Hearing initially appears normal in young DFNA20/26 individuals and begins to deteriorate at high frequencies in the 1st to 3rd decade of life followed by nearly complete hearing loss at all tested frequencies by the 4th to 6th decade. Distortion product otoacoustic emissions are absent in individuals with the p.T89I mutation (Elfenbein et al, 2001), which may indicate loss of cochlear amplification due to a malfunction of outer hair cells. Given that hearing appears normal in the 1st decade in most DFNA20/26 subjects, one possibility is that ACTG1 mutations somehow affect durability of actin structures and/or interfere with a repair process.…”

A Dutch Family With Hearing Loss Linked to the DFNA20/26 Locus

“…Figure 4 shows the age-related typical audiograms of the present family and, for the sake of comparison, of a known DFNA20 family. 13 The plots in Figure 5 combine the longitudinal analyses in the suitable cases with the (cross-sectional) data in the other cases. Cross-sectional data reported by Elfenbein et al 13 are included for the purpose of comparison.…”

“…Statistical analysis was performed on pure-tone audiometry data and on speech-recognition scores. The results were compared with those previously reported for 4 affected family members of a known DFNA20 family 13 ; speech recognition scores were compared with those found in subjects with DFNA2, 8 DFNA5, 9 DFNA9, 8 and presbyacusis. 14…”

A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26)

“…For individual autosomal dominant families it is often possible to suggest one or a few loci or genes that may be involved, through cross sectional or longitudinal analysis of audiograms of several family members. 4 5 Four families with autosomal dominant postlingual sensorineural hearing loss were found to be linked to overlapping regions of chromosome 17q25, [6][7][8][9] and two different DFNA locus numbers (DFNA20 and DFNA26) were assigned to this region. We recently described a fifth Dutch family with linkage to this interval.…”

“…The hearing loss in this family is very similar to that in the family described by DeWan et al 9 Although hearing loss in the original DFNA20 family follows a less severe course, the progression is highest for 8 kHz, followed by 4, 2, and 1 kHz. 7 In this paper we describe candidate gene analysis in the Dutch family, which led to the identification of a missense mutation in the ACTG1 gene which encodes c-actin 1. Using the structure of the highly homologous Mg 2+ -ATP actin 1 of Dictyostelium discoideum, we provide evidence that the missense mutation has a small but significant functional effect.…”