Mapping and Cloning Hereditary Hearing Impairment Genes

Friedman, Thomas Baer

Abstract

Hearing loss loci segregating in consanguineous families from India and Pakistan were ascertained. Each family consisted of at least three affected children related to each other through at least one consanguineous union. Some of these families mapped to known loci such as DFNB3, DFNB4, DFNB6, DFNB7/DFNB9, DFNB8/DFNB10 and DFNB12. Others represent mutations in new DFNB genes that are being mapped. The new locus DFNB29 (found at 21q22) was mapped this past year in two large consanguineous families from Pakistan and the responsible gene was cloned. This manuscript is in preparation. An oral presentation of this work will be given during the upcoming meeting of the American Society of Human Genetics in early October (abstract 18, Molecular Basis of Mendelian Disorders I, session 14). Much progress has been made on the DFNB26 locus on chromosome 4q31. A manuscript is in preparation describing this interesting locus which has a mapped modifier locus on chromosome 1q23. The dominant modifier, DFNM1, protects family members from DFNB26 hearing impairment. An oral presentation of this work will be given during the upcoming meeting of the American Society of Human Genetics (abstract 56, Linkage mapping and polymorphisms I, session 18). Genome-wide scans are being performed on many consanguineous families that are not linked to known deafness causing loci.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute on Deafness and Other Communication Disorders (NIDCD)
• Type: Intramural Research (Z01)
• Project #: 1Z01DC000035-04
• Application #: 6431979
• Study Section: (LMG)
• Support Year: 4
• Fiscal Year: 2000

Institution

• Name: Deafness & 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

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

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