AUTOSOMAL-DOMINANT, PRELINGUAL, NONPROGRESSIVE SENSORINEURAL HEARING-LOSS - LOCALIZATION OF THE GENE (DFNA8) TO CHROMOSOME 11Q BY LINKAGE IN AN AUSTRIAN FAMILY

A four-generation family suffering from an autosomal-dominant, congeni tal, nonprogressive, nonsyndromic hearing loss was found in a rural re gion of Austria. The hearing loss was moderate to severe, a pure tone audiogram showing a U-shaped form with maximum loss at 2,000 Hz. An in itial genome search led to a lod score of 3.01 with markers on chromos ome 15. This locus was registered as DFNA8 in the HUGO data base. Furt her sampling of the family, however, yielded data that reduced the max imal lod score with chromosome 15 markers to 1.81. The genome search w as restarted using an ABI(TM) genotyper, which eventually detected sev eral positive two-point lod scores with markers from the long arm of c hromosome 11. The highest value was 3.6, which was seen with the marke r D11S934. Haplotype analysis excluded the gene from the chromosomal r egion proximal from D11S898 and distal to D11S1309. These results plac e the gene in the region of the hearing loss gene DFNA12. Recent evide nce suggests that the somewhat different phenotypes found in these two families are due to two different mutations in the human alpha-tector ine gene (Verhoeven et al., 1998).