The Unit conducted collaborative research projects, provided cytogenetic services for NIH patients, and participated in the NIH Medical Genetics Training and College of America Pathologists proficiency testing programs. Case studies were from protocols for short stature, premature ovarian failure (POF), Turner syndrome (TS), mental handicaps, recognized dysmorphic syndromes, neurological diseases, and neoplasia. Detection of aberrations which might lead to mapping of disease genes was a frequent indication of cytogenetic evaluation. Both traditional methods and fluorescent in-situ hybridization (FISH) were used to identify abnormalities. Numerical and structural sex chromosomal abnormalities (SCA) were the most frequent variations among 186 new cases. Of 128 TS patients studied, 65% were nonmosaic 45X and 35% were genetic variants. Studies of cognition, visuospatial ability, and CNS structural variation in 9 subjects were reported. Significant differences were observed only in nonmosaics. Additional brain metabolic and neuropsychological studies of TS are being reported. Separate comparison of nonmosaics and genetic variants with controls resulted in more accurate data for genetic counseling in TS. Screening of 166 POF patients revealed SCA in 2.8%, and 3% were familial. From our previous report of familial POF, our molecular analysis of an X; autosome translocation, and review of other genetic studies of POF, we suspect there are 2 critical regions for ovarian failure; Xq13.3-q21.1 and zq26.1-q27. Molecular studies of these regions in familial POF may lead to development of DNA probes for presymptomatic diagnosis in these families or permit detection of microdeletions in cytogenetically normal patients with sporadic POF. We are continuing to evaluate patients with childhood schizophrenia and Fragile X syndrome, and several of these studies are being published. Also, the NCHGR is now actively involved in cytogenetic research at NIH, and we plan to interact with their investigators in our studies and genetics training program activities.
