A further refinement of linkage data on nonsyndromic hereditary hearing impairment has occurred in a family with X-linked hearing impairment. This family is linked to markers in the Xp21.2 region. The same region contains the Duchenne Muscular Dystrophy locus. However, this family shows no evidence of muscular dystrophy. The International Waardenburg Syndrome Consortium has found that all families with Waardenburg syndrome type I are linked to the PAX3 gene at 2q35-q37. They have also found that the presence of dystopia canthorum in multiple family members is a reliable indication for identifying families likely to have a defect in the PAX3 gene. LMG scientists have found, in cooperation with two other member groups of the Waardenburg consortium, that three of eight families with Waardenburg syndrome type II are linked to the 1p13.3-2.1 region. Also, one of the eight families is linked to the Mi locus on 3p14.1-p12.3. LMG has described some of the first mutations found in the homeodomain of the PAX3 gene in humans as part of our efforts to define the intron/exon boundaries to the homeodomain region of exons five and six from the PAX3 gene. A cDNA library made from guinea pig crista ampullaris has been distributed to other investigators. This cDNA library represents the organ of balance in the inner ear and should prove to be important in defining the genes responsible for balance. We continue to work with an organ of Corti cDNA library which should provide us with unique clones to the organ of hearing. In addition to a novel zinc finger transcription factor, a clone unique to neuronal tissues has been found. Additional unique clones to the inner ear are being sought.
