The unit provided cytogenetic services for NIH patients, participated in the Interinstitute Medical Genetics Training and College of American Pathologists proficiency testing programs, responded to public inquiries, and collaborated in research projects. The patient database of 1,300 includes many with short stature, premature ovarian failure (POF), Turner syndrome (TS), endocrine disorders, mental handicap, recognized syndromes, and neurological disease. Our studies were requested to determine protocol eligibility, identify genetic variants, diagnose syndromes, and detect aberrations to localize disease genes. Controlled studies of rRNA gene activity in Alzheimer's disease and normal aging were reported. Variations in structure and activity, measured by silver staining of chromosomal rDNA and protein (NORs), were found to be not associated with disease or aging. We then studied cytogenetic variation in 116 TS patients; 35% were genetic variants and 65% typical nonmosaic 45, X. Fluorescent In-Situ Hybridization (FISH) and X-and Y-specific DNA probes was required for identification of 4 variants. Controlled CNS imaging and cognitive studies of 18 of the TS patients were reported; significant differences were found, and nonmosaics were more affected than mosaics. Of 153 POF patients, 5% were familial, and 2% had abnormal karyotypes, including one with an X; autosome rearrangement. Her molecular studies suggested a critical locus within proximal Xq. Probes from this and a more distal Xq critical region might detect microdeletions in karyotypically normal familial POF. We also evaluated autistic savants and childhood schizophrenics for dysmorphic features and karyotypic abnormalities. These were done to better define the disorders physically and detect aberrations for disease gene localization. As medical genetics training and research at NIH expand. We expect to continue our clinical services, interaction with the medical genetics training program, and collaborative projects.
