Hereditary Waardenburg syndrome, which in its varying expression includes a hearing impairment is being studied. Findings of the International Waardenburg Syndrome Consortium suggest that the syndrome is linked to the gene PAX3 in less than 50% of families but do not suggest any association between the clinical outcome and the-molecular pathology in 12 families with known mutations. We have shown that there are 3 introns within the PAX3 gene' s putative exon 5 which indicates that PAX3 has 8 exons. In the work on Nonsyndromic hereditary hearing impairment we have identified a family with X-linked hearing impairment. Using polymorphic linkage markers for typing DNA from family members we conclude that the disease gene is linked to the short arm of the X chromosome, to Xp11.3-2l. The study of the Bronx Waltzer mouse strain to characterize the gene bv, which underlies the deafness of this mouse, has continued. We have shown that bv is located on the long arm of chromosome S. A human family for which the Bronx Waltzer may be a model has been described by others. We are continuing to work on defining the bv gene. A mouse with a transgenic insertional mutation that causes an inner ear disorder is also continuing to be studied. It has been shown in a collaborating laboratory, LVMP, NINDS, that the insertional mutation has affected the gene mi. This gene is expressed intensely in melanocytes of tissues, including the otic vesicle. These mice are potentially valuable models for certain types of hereditary hearing impairment in humans. Last year a cDNA library based on the mRNAs from the auditory sensory organ was constructed. We have cloned a gene from this library that encodes for a novel member of the zinc finger transcription factor family. We have shared this cDNA library with the auditory research community.
