Cloning Hereditary Hearing Impairment Genes Segregating in Families

Friedman, Thomas Baer

Abstract

of Work: The DFNB7 locus was initially mapped in two families from India. These two families made it possible to localize the gene within a 4 cM region of chromosome 9q11-q21. This region is syntenic to mouse chromosome 19 to which the deafness (dn) locus was mapped by Dr. Bronya Keats, LSU Medical Center, New Orleans LA. We have constructed a BAC contig through one of the dn chromosomal inversion breakpoints and sample sequencing has been performed in an effort to localize candidate cDNA molecules in the region of interest. Candidate genes will be tested against DNA from the dn mouse isolated in the laboratory of Dr. Steel. In 1993, four families in India were identified as being suitable for linkage analysis. Each family consisted of at least four affected children related to each other through a consanguineous union. Two families mapped to DFNB3; one family provided information for localization of the DFNB7 locus; and the fourth family is linked to a new locus, DFNB18. The information for the DFNB18 locus will be submitted for publication in the near future. Several additional Indian families have recently been identified which support LOD scores over 3 with nonsyndromic hereditary hearing impairment. DNA samples from these families are being analyzed for localization to known loci. Any families unlinked to the known loci will then be mapped to find additional locations for recessive loci causing nonsyndromic hereditary hearing impairment. The Center for Excellence in Molecular Biology in Pakistan has identified two very large consanguineous families with nonsyndromic hereditary hearing impairment. DNA from these families will also be collected and studied. There are multiple families in a small region of Newfoundland which have a high proportion of deaf children. Efforts are being made to collect appropriate phenotype data on these families. Most of the DNA samples from the area have been received. Mapping efforts in these families are inconclusive to date.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute on Deafness and Other Communication Disorders (NIDCD)
• Type: Intramural Research (Z01)
• Project #: 1Z01DC000035-01
• Application #: 6161761
• Study Section: Special Emphasis Panel (LMG)
• Support Year: 1
• Fiscal Year: 1997

Institution

• Name: National Institute on Deafness and Other Communication Disorders
• Country: United States

Publications

Collin, Rob W J; Kalay, Ersan; Tariq, Muhammad et al. (2008) Mutations of ESRRB encoding estrogen-related receptor beta cause autosomal-recessive nonsyndromic hearing impairment DFNB35. Am J Hum Genet 82:125-38

Liburd, N; Ghosh, M; Riazuddin, S et al. (2001) Novel mutations of MYO15A associated with profound deafness in consanguineous families and moderately severe hearing loss in a patient with Smith-Magenis syndrome. Hum Genet 109:535-41

Ahmed, Z M; Riazuddin, S; Bernstein, S L et al. (2001) Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F. Am J Hum Genet 69:25-34

Ben-Yosef, T; Wattenhofer, M; Riazuddin, S et al. (2001) Novel mutations of TMPRSS3 in four DFNB8/B10 families segregating congenital autosomal recessive deafness. J Med Genet 38:396-400

Riazuddin, S; Castelein, C M; Ahmed, Z M et al. (2000) Dominant modifier DFNM1 suppresses recessive deafness DFNB26. Nat Genet 26:431-4

Friedman, T B; Hinnant, J T; Fridell, R A et al. (2000) DFNB3 families and Shaker-2 mice: mutations in an unconventional myosin, myo 15. Adv Otorhinolaryngol 56:131-44

McGuirt, W T; Lesperance, M M; Wilcox, E R et al. (2000) Characterization of autosomal dominant non-syndromic hearing loss loci: DFNA 4, 6, 10 and 13. Adv Otorhinolaryngol 56:84-96

Yasunaga, S; Grati, M; Chardenoux, S et al. (2000) OTOF encodes multiple long and short isoforms: genetic evidence that the long ones underlie recessive deafness DFNB9. Am J Hum Genet 67:591-600

Friedman, T; Battey, J; Kachar, B et al. (2000) Modifier genes of hereditary hearing loss. Curr Opin Neurobiol 10:487-93

Wilcox, E R; Everett, L A; Li, X C et al. (2000) The PDS gene, Pendred syndrome and non-syndromic deafness DFNB4. Adv Otorhinolaryngol 56:145-51