Localization of a novel gene for nonsyndromic hearing loss (DFNB17) to chromosome region 7q31

Abstract

Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of hereditary hearing impairment (HHI). To date, 16 different loci have been reported, making ARNSHL an extremely heterogeneous disorder. One of these loci, DFNB4, was mapped to a 5-cM interval of 7q31 in a large Middle-Eastern Druze family. This interval also includes the gene for Pendred syndrome. We report on three new families with HHI from the Madras region of southern India that demonstrate linkage to 7q. Their pedigrees are compatible with autosomal recessive inheritance. Furthermore, the largest family identifies a novel locus (DFNB17) telomeric to the DFNB4 and Pendred intervals. A 3-cM region of homozygosity by descent between markers D7S486 and D7S2529 is present in all affected individuals in this family and generates a multipoint LOD score of 4.24. The two other families map to the previously reported DFNB4 region but have insufficient power to attain significant LOD scores. However, mutations in the Pendred syndrome gene are present in one of these families.

A mutation ofMET, encoding hepatocyte growth factor receptor, is associated with humanDFNB97hearing loss

“…This locus was designated DFNB97 by the HUGO Gene Nomenclature Committee. DFNB97 overlaps with the originally reported interval for the DFNB17 6 locus (OMIM 603010). However, the DFNB17 interval was subsequently refined7 to a non-overlapping 5.5-Mb region centromeric of DFNB97 .…”

Contribution of connexin26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India

“…Seven deafness loci are currently known to be associated with deafness in India. These include DFNB3, 4 DFNB5, 5 DFNB6, 6 DFNB7/B11, 7 DFNB15, 8 DFNB17, 9 and DFNB18. 10 In four of these seven cases, the associated gene has been cloned: transmembrane cochlear expressed gene 1 (TMC1) for DFNB7/B11, 11 myosin XVA (MYO15A) for DFNB3, 4 12 transmembrane inner ear expressed gene (TMIE) for DFNB6, 13 and harmonin for DFNB18.…”

The <i>PDS</i> Gene, Pendred Syndrome and Non-Syndromic Deafness (DFNB4)

“…For example, DFNB13 maps to 7q34-36, approximately 30 cM telomeric to PDS [38]. DFNB17 maps to 7q31, approximately 7 cM telomeric to PDS [39]. Of interest, a family with profound prelingual, non-syndromic deafness in Madras (India) showed genetic linkage to the PDS gene but not to either the DFNB13 or DFNB17 regions; however, no PDS mutations were found in this family [39].…”