Refining the DFNB7-DFNB11 deafness locus using intragenic polymorphisms ina novel gene, TMEM2

The combined DFNB7-DFNB11 deafness locus maps to chromosome 9q13-q21 betwee n markers D9S1806 and D9S769. We have determined the cDNA sequence and geno mic structure of a novel gene, TMEM2, that maps to this interval and is exp ressed in the cochlea. The mouse orthologue of this gene (Tmem2) maps to th e murine dn (deafness) locus on mouse chromosome 19. Screens for transmembr ane helices reveal the presence of at least one putative transmembrane doma in in the TMEM2 protein. To determine whether mutations in TMEM2 cause hearing loss at the DFNB7-DFN B11 locus, we screened the coding region of this gene in DFNB7-DFNB11 affec ted families by direct sequencing. All DNA variants that segregated with th e deafness and changed the predicted amino acid sequence of TMEM2 were comm on polymorphisms, as demonstrated by allele-specific amplification of poole d control DNA. Northern blot analysis showed no difference in transcript si ze or expression level of Tmem2 in dn/dn and control mice. The intragenic p olymorphisms in TMEM2 represent a novel centromeric boundary for the DFNB7- DFNB11 interval, (C) 2000 Elsevier Science B.V. All rights reserved.