Hereditary postlingual sensorineural hearing loss mapping to chromosome Xq21

Background: Mutations on the X-chromosome clinically manifesting different phenotypes of hearing loss have been mapped to the long arm at different lo ci, DFN1-DFN3. Another defect in a family with sex-linked, postlingual, pro gressive sensorineural hearing loss was mapped to Xq. Methods: Clinically, the family was evaluated by physical and audiometric e xamination of 17 members including computerized tomographic (CT) evaluation of the proband. Molecular evaluation consisted of polymerase chain reactio n amplification of patient genomic DNA and resolution P-32-labeled fragment s by polyacrylamide gels. Inheritance of DNA alleles and deafness were anal yzed using the MLINK computer program. Results: Five affected males demonstrated symmetrical sensorineural hearing loss as significant as 100 decibels (dB). Two carrier females had a milder loss with frequency findings of 10 dB to 60 dB. Computerized tomography (C T) evaluation of the temporal bones of the proband was normal. The odds wer e 200:1 that the responsible gene was linked to locus DXS986 (maximum lod s core = 2.3 at theta = 0). Analysis of recombination events defined by famil y members demonstrates that the responsible gene lies in a 21 cM (30 MB) in terval, between loci DXS12175 and 1106. The disease locus in this family do es not appear to map to DFN1 or DFN3. Conclusion: The family described here, with affected males who have progres sive, postlingual sensorineural hearing loss and mildly affected females ma ps most compatibly to the DFN2 locus. Analysis of hereditary deafness in th is family refines the DFN2 locus to a 9.2 Mb region in chromosome X band q2 1 between DXS990 and DXS1106.