A Dutch family with progressive autosomal dominant non-syndromic sensorineural hearing impairment linked to DFNA13

Abstract

We present a Dutch family with autosomal dominantly inherited mid-frequency and high-frequency sensorineural hearing impairment. Genetic linkage analysis in this family indicated linkage to DFNA13 with logarithm of the odds ratio (LOD) scores > +4. The majority of the affected persons presented with hearing impairment from the age of 30 years onwards, although hearing impairment was noted at about 10 years of age in two affected persons. Three individuals represent phenocopies. After correction for presbyacusis, hearing impairment was most marked at 1-2 kHz and showed an annual progression of 0.8 dB per year. By the age of 60 years, the configuration of the audiogram was flat, reflecting the combined effects of the inherited progressive hearing loss and presbyacusis. Vestibular function was intact. Recently, mutations in the COL11A2 gene were found in two other families with non-syndromic hearing impairment linked to DFNA13. Further mutation analysis of the COL11A2 gene will show whether this family also contains a COL11A2 mutation.

Nuclear and mitochondrial genes mutated in nonsyndromic impaired hearing

“…By age 60 years, the configuration of the audiogram was flat, reflecting the combined effects of the inherited progressive hearing loss and presbyacusis. Vestibular function was intact [40,41].…”

Flat Threshold and Mid-Frequency Hearing Impairment in a Dutch DFNA8/12 Family with a Novel Mutation in <i>TECTA</i>

“…Genotyping such traits succeeded within the decade around the past turn of the century.Hereditary mid-frequency hearing impairment has been diagnosed in families with DFNA8/12, DFNA13, DFNA21, DFNA31, DFNA44, DFNA49 [Brown et al, 1997;Ensink et al, 2001;Kirschhofer et al, 1998;Kunst et al, 2000;McGuirt et al, 1999;Moreno-Pelayo et al, 2003;Snoeckx et al, 2004;Van Camp et al, 1997;Verhoeven et al, 1997Verhoeven et al, , 1998] and more recently in some cases of DFNA15 [Pauw et al, 2008], as well as in a family that carries a mutation in the Wolfram syndrome type 1 gene (WFS1). The latter gene is involved in DFNA6/14/38 [Fujikawa et al, 2007] and in the Wolfram syndrome.…”

A novel locus for autosomal dominant non-syndromic hearing loss, DFNA31, maps to chromosome 6p21.3

“…Clinical investigations of this family have been reported by Ensink et al 7 Briefly, hearing impairment in the family is, apart from presbyacusis, most pronounced at 1 to 2 kHz. On the basis of audiograms and clinical investigations, 12 individuals were classified as affected and included in the linkage analysis.…”

“…Filled symbols represent individuals with hereditary hearing impairment and empty symbols represent individuals with normal hearing. In order to allow detailed comparisons of genotypes and phenotypes, the numbering of family members is the same as in the previous clinical description of this family 7. Haplotypes for the markers of table 1 are given below each symbol.…”