Hereditary nonsyndromic hearing loss (NSHL) is extremely heterogeneous.During the past decade, remarkable progress has been made towards determining the deafness-causing genes.To date, over 110 loci have been mapped for NSHL, and 47 deafness genes from these loci have been identified.The vast majority of cases of NSHL are associated with mutations in autosomal genes.Xlinked deafness is clinically and genetically a heterogeneous disorder accounting for about 5% of all congenital deafness, and for less than 2% of non-syndromic hearing impairment.The first deafness-causing gene, POU3F4, was identified in a family with X-linked non-syndromic hearing loss in 1995.Although seven non-syndromic deafness loci (DFN2-8) have been mapped to the X chromosome over the last 15 years, the second X-linked deafness gene has not yet been identified.The DFN2 locus was mapped to Xq13-q24 and previously defined by three different families.The age at detection of the hearing loss in affected males in these families varied from birth to 20 years of age, indicating that DFN2 can cause either congenital or post-lingual deafness.In the present study, we ascertained a five generation Chinese family characterized by X-linked postlingual, progressive, non-syndromic sensorineural hereditary heating impairment.We mapped the disease locus to a 5.4 cM region on Xq22 between DXS8020 and DXS8055 overlapping with the known DFN2 locus.Mutations in the phosphoribosyl pyrophosphate synthetase 1 (PRPS1) gene were found in all identified DFN2 families, demonstrating that PRPS1 is likely the gene responsible for DFN2 deafness.