candidate's description): The Smith-Magenis syndrome (SMS) is a multiple anomaly, mental retardation syndrome associated with a deletion of chromosome 17 band p11.2. Characteristic features include short stature, dysmorphic facial appearance, brachydactyly, behavioral problems, and sleep disturbances. SMS individuals can also be affected with ophthalmic, otolaryngologic, cardiac and renal anomalies. Although SMS is considered to be a contiguous gene deletion syndrome caused by haploinsufficiency of many physically contiguous but functionally unrelated loci, the molecular etiology remains unknown. There is phenotypic variation among SMS individuals suggesting the presence of recessive alleles or modifier loci within this region. Currently, only a few genes have been mapped to the SMS region and their contribution to this complex phenotype remains speculative. The candidate proposes to isolate and characterize genes within the SMS critical region, and elucidate any genotype/phenotype correlation in SMS. She also proposes to further characterize the genomic structure and mechanism of deletion of this region. SMS patients are followed at the Texas Children's Hospital Genetic Clinic and others are referred for consultation and clinical research through the General Clinical Research Center for Children (GCRC) by colleagues across the country. Cell lines are established on 86 SMS patients, and a YAC contig spanning the SMS region is being developed.
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