A wide range of cytogenetic methods were utilized for patient investigations in order to correlate specific chromosomal variations with phenotypic abnormalities. Patients with Alzheimer's disease, trisomy 21 and other recognized syndromes, and parents of children with trisomy 21 were studied. We began cytogenetic evaluations of other Clinical Center patients, when the Medical Genetics Program assumed this responsibility in December, 1986. Our controlled investigations of Alzheimer's disease and older Down syndrome patients with dementia are nearly completed. The only specific variation correlated with dementia was typical constitutional trisomy 21; secondary aberrations observed were probably age- rather than disease-specific. These results are consistent with recent molecular analyses, which indicate that microduplications or other genetic abnormalities of chromosome 21 are associated with dementia of the Alzheimer type. Our analysis of ribosomal DNA gene expression of the nucleolus organizing regions (NOR) of these subjects will soon be completed; the results will be correlated with age and clinical status and compared with control subjects. Our analysis of the NOR in parents of Down syndrome patients is complete; NOR duplication (dNOR variant) reported by others to be frequent in such parents, predisposing to trisomy 21, was not observed. High-resolution collaborative studies of several recognized syndromes with suspected deletions were recently initiated; data will be collected during the coming year. In situ hybridization experiments with high-resolution chromosome preparations and previously localized probes are in progress, and collaborative experiments with unmapped DNA probes will soon be attempted. Among clinical center patients evaluated with the Medical Genetics Program, abnormal karyotypes and conspicuous variants were frequent (29%). This suggests that many active clinical protocols concern subjects with chromosomal abnormalities or require differentiation between cytogenetic and other genetic etiologies.
