DFNA49, a novel locus for autosomal dominant non-syndromic hearing loss, maps proximal to DFNA7/DFNM1 region on chromosome 1q21-q23.

A pproximately 1 in 1000 children is born with a serious permanent hearing impairment (pre-lingual deafness), and it is estimated that more than half of these cases in developed countries are due to genetic factors. The prevalence of hearing loss increases dramatically with age; it is estimated that approximately 5% of people under 45 years of age have a significant loss of hearing, increasing to approximately 50% by 80 years of age. Age related late onset hearing loss (presbycusis) is a heterogeneous trait with many suspected causes. Genetic or environmental factors such as diabetes, mitochondrial mutations, or environmental noise exposure may contribute to the trait. In addition, hearing loss beginning at late childhood, youth, or later, clearly segregates as a monogenic autosomal dominant Mendelian trait in many families. The hearing loss phenotype in these families is usually non-syndromic—that is, the hearing loss is not associated with other anomalies, and it accounts for up to 20% of the cases of non-syndromic sensorineural inherited deafness. This type of hearing loss is usually progressive, affecting a particular range of frequencies in each case. To date, 36 loci for autosomal dominant non-syndromic sensorineural hearing loss (ADNSSHL) have been mapped, and 17 deafness genes from these loci have been identified. These genes encode a wide variety of proteins; some have known function but for most, the underlying mechanisms leading to hearing impairment are uncertain. Given the few described mouse models for progressive hearing loss, our current understanding of post-lingual and progressive deafness relies on the identification of genes through human mapping studies. In this work we describe the mapping of a novel DFNA locus on chromosome 1q21–q23 segregating in a Spanish family with post-lingual and progressive hearing loss.