Dominant modifier DFNM1 suppresses recessive deafness DFNB26.
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.
Riazuddin
S
S
Laboratory of Molecular Genetics, NIDCD/NIH, Rockville, Maryland, USA.
Castelein
C M
CM
Ahmed
Z M
ZM
Lalwani
A K
AK
Mastroianni
M A
MA
Naz
S
S
Smith
T N
TN
Liburd
N A
NA
Friedman
T B
TB
Griffith
A J
AJ
Riazuddin
S
S
Wilcox
E R
ER
D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D000072259:Connexin 26; D017630:Connexins; D003241:Consanguinity; D003638:Deafness / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D013489:Suppression, Genetic
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26