Dominant modifier DFNM1 suppresses recessive deafness DFNB26

Nat Genet. 2000 Dec;26(4):431-4. doi: 10.1038/82558.

Abstract

More than 50% of severe childhood deafness is genetically determined, approximately 70% of which occurs without other abnormalities and is thus termed nonsyndromic. 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), pendrin, otoferlin and alpha-tectorin, 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 theta=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 theta=0 for D1S2815.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Mapping
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 4 / genetics
  • Connexin 26
  • Connexins
  • Consanguinity
  • Deafness / genetics*
  • Female
  • Genes, Dominant
  • Genes, Recessive
  • Haplotypes
  • Humans
  • Lod Score
  • Male
  • Microsatellite Repeats
  • Pedigree
  • Suppression, Genetic

Substances

  • Connexins
  • GJB2 protein, human
  • Connexin 26