We have continued a study of the hereditary Waardenburg syndrome, which in its varying phenotype includes a hearing impairment. We have initiated the forming of an international Waardenburg Syndrome Consortium consisting of 6 research teams. The teams' pool results from linkage studies with a series of nucleotide probes. It has been established that the Waardenburg syndrome is caused by defects at multiple loci, one of which is between ALPP and FN1 on chromosome 2. We have shown that the human gene Hup2 is located within 350,000 base pairs of Waardenburg syndrome Type 1 gene as it is expressed in a cell line from a child with a de novo inversion of 2q35- q37 and a de novo expression of the syndrome. In collaboration with the Laboratory of Viral and Molecular Pathogenesis (LVMP), NINDS, NIH we are studying mice with a transgenic insertional mutation that has caused an inner ear disorder associated with a melanocyte anomaly. We are continuing our study of hereditary deafness in the Bronx Waltzer, a strain of mouse with the mutant gene bv that is autosomal, recessive, with full penetrance. We are crossing bv mice with MEV mice from a mouse linkage testing stock possessing multiple copies of the endogenous ectotrophic murine leukemia genome. In this study, we collaborate with Dr. C.T. Hansen, VRB, NCRR, NIH and Dr. B.A. Taylor, Jackson Laboratory, Bar Harbor, Maine. Our study of G protein-coupled receptors in the cochlea of mice and of guinea pigs continues and includes amplification using PCR. To date, we have obtained two new putative members of this family. Related to this, we are attempting to define at the molecular level G proteins in the cochlea. This study is in progress. We are initiating a study of non-syndromic sensory neural hearing impairments, aiming at defining at the molecular level genes that cause such conditions.
