In cooperation with the medical genetics program, our cytogenetic studies of 225 new clinical center patients were retrieved from a database for correlation with clinical status. Chromosomal abnormalities were most frequent in patients with admitting diagnoses of hypogonadism or infertility (22.7%) and common in patients with short stature (5.6%) and premature ovarian failure (5.6%). Of over 60 Turner syndrome patients screened, nearly 70% were 45,X and the remainder were either mosaics or had structurally abnormal X chromosomes. High-resolution karyotypes were normal in patients with primary diagnoses of metabolic disease and seizure disorder, as well as in patients with isolated aniridia, Von-Hippel Lindau disease, and Lowe's syndrome. Three of 6 patients with the Prader-Willi syndrome had deletions involving bands q11.1 to ql3 of chromosome 15, consistent with other reported studies of this syndrome and with a recent report of maternal uniparental disomy in Prader-Willi patients without deletions. Complex rearrangements were found in one autistic patient and one patient with the Russell-Silver phenotype, providing clues for localization of genetic changes in these syndromes. Several patients studied by our laboratory were described in case reports, including mosaic translocation trisomy 21 in a non-mentally retarded woman with Alzheimer's disease, an individual with 47, XXX Klinefelter syndrome and a conduct disorder, and a patient with familial carotid body tumors and extra-adrenal pheochromocytomas. Levels of expression of the fragile X chromosome in peripheral blood were determined for a group of young adult males with typical fragile X syndrome in collaboration with the NIA as part of their studies of the CNS in this disorder, which will soon be reported. During the coming year, we plan to take part in collaborative investigations of familial premature ovarian failure and of the 18p- syndrome. These studies will emphasize localization of genes responsible for the different clinical manifestations of these syndromes.
