The unit conducted collaborative research projects, provided cytogenetic services for NIH patients, and participated in the NIH Medical Genetics Training and College of American 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 for cytogenetic evaluation. Both traditional methods and fluorescent in-situ hybridization (FISH) were used to identify abnormalities. Numerical and structural sex chromosomal abnormalities were the most frequent variations among 293 new cases. Of all 194 TS patients now screened, 70% were nonmosaic 45,X; the remainder had mosaicism or had X structural abnormalities. Controlled neuropsychological studies in one group of subjects revealed significant abnormalities only in nonmosaics. A controlled longitudinal study comparing mosaic and nonmosaic TS subjects recently reported by other investigators gave similar results. These results will aid in genetic counseling for TS, particularly when detected prenatally, and for establishing prognosis. Of 187 POF patients now screened, only 3 had abnormal karyotypes. From our previous study of familial POF, our molecular analysis of an X;autosome translocation and literature review, we suspect there are 2 critical regions within Xq for ovarian failure: Xql3.3-q2l.l and Xq26.l-q27. Molecular studies of these regions in familial POF, including a search for Fragile X premutations within the FMRI gene at Xq27.3, may lead to development of DNA probes for presymptomatic diagnosis. We are continuing to screen patients with childhood schizophrenia for cytogenetic abnormalities to evaluate an association with deletions of chromosome 22q11.2 reported elsewhere. In a small group of previously karyotyped patients with short stature, screening for uniparental disomy (UPD) of several different autosomes was initiated to determine if certain growth retardation syndromes are associated with this phenomenon. In all of these studies, we interact with the Molecular Cytogenetics Laboratory, DDB, NCHGR.
