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Dominant modifier DFNM1 suppresses recessive deafness DFNB26

Abstract

More 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 α-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 θ=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 θ=0 for D1S2815.

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Figure 1: DFNB26-linked haplotypes of PK2 family members on chromosome 4q31.
Figure 2: DFNM1-linked haplotypes of PK2 family members on chromosome 1q24.
Figure 3: Representative pure-tone audiograms for PK2 family members.

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Acknowledgements

We thank the PK2 family members for their participation, which is supported by the National Institute on Deafness and Other Communication Disorders, Intramural Research Project Z01DC00035; B.U. Amjad for help in initiating this study; R. Morell, D. Drayna, J. Bork, T. Ben-Yosef and K. Kurima for comments; and S. Khan and B. Ploplis for technical support. University Grants Commission supported part of this study in Pakistan. This study used the computational capabilities of the Biowoulf Center at the CIT, NIH.

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Correspondence to Edward R. Wilcox.

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Riazuddin, S., Castelein, C., Ahmed, Z. et al. Dominant modifier DFNM1 suppresses recessive deafness DFNB26. Nat Genet 26, 431–434 (2000). https://doi.org/10.1038/82558

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