Nature Genetics
26, 431 - 434 (2000)
doi:10.1038/82558
Dominant modifier DFNM1 suppresses recessive deafness DFNB26Saima Riazuddin1, 2, Caley M. Castelein3, Zubair M. Ahmed1, 2, Anil K. Lalwani3, Mary A. Mastroianni4, Sadaf Naz2, Tenesha N. Smith1, Nikki A. Liburd1, Thomas B. Friedman1, Andrew J. Griffith1, 4, Sheikh Riazuddin2
& Edward R. Wilcox11
Laboratory of Molecular Genetics, NIDCD/NIH, Rockville, Maryland, USA. 2
Center of Excellence in Molecular Biology, Punjab University, Lahore, Pakistan. 3
Laboratory of Molecular Otology, Department of Otolaryngology, University of California, San Francisco, California, USA. 4
Neuro-Otology Branch, NIDCD, NIH, Bethesda, Maryland, USA.
Correspondence should be addressed to Edward R. Wilcox wilcoxe@nidcd.nih.govMore than 50% of severe childhood deafness is genetically determined, approximately 70% of which occurs without other abnormalities and is thus termed nonsyndromic1,
2. So far, 30 nonsyndromic recessive deafness loci have been mapped and the defective genes at 6 loci, DFNB1, DFNB2, DFNB3, DFNB4, DFNB9 and DNFB21, have been identified, encoding connexin-26 (ref. 3), myosin VIIA (ref. 4), myosin XV (ref. 5), pendrin6, otoferlin7 and  -tectorin8, respectively. Here we map a new recessive nonsyndromic deafness locus, DFNB26, to a 1.5-cM interval of chromosome 4q31 in a consanguineous Pakistani family. A maximum lod score of 8.10 at  =0 was obtained with D4S1610 when only the 8 affected individuals in this family were included in the calculation. There are seven unaffected family members who are also homozygous for the DFNB26-linked haplotype and thus are non-penetrant. A dominant modifier, DFNM1, that suppresses deafness in the 7 nonpenetrant individuals was mapped to a 5.6-cM region on chromosome 1q24 with a lod score of 4.31 at =0 for D1S2815.
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