QUANTIFICATION BY FLOW-CYTOMETRY OF CHROMOSOME-17 DELETIONS IN SMITH-MAGENIS SYNDROME PATIENTS

We have used bivariate flow karyotyping to quantify the deletions invo lving chromosome 17 in sixteen patients with Smith-Magenis syndrome (S MS). The fluorescence intensities of mitotic chromosomes stained with Hoechst 33258 and chromomycin were quantified in a dual-beam flow cyto meter. For each patient, the position of the peak representing the del eted chromosome 17 was compared to those of the normal homologs of an unaffected parent. The patients could be classified into four groups b ased on the size of their deletions. The deletions ranged from similar to 9-10 Mb (similar to 10-11% of the chromosome) to below the detecti on limit of the technique (2 Mb). Different deletion sizes were detect ed among patients whose high-resolution banding results were similar. Some deletions detected by banding were not detected by flow analyses. Deletion estimates are largely consistent with the results of molecul ar analyses. Patients with larger deletions that extend into band 17p1 2 have abnormal electrophysiologic studies of peripheral nerves. Delet ion size does not appear to correlate with the degree of mental retard ation, presence of behavioral abnormalities, craniofacial anomalies or common skeletal findings in SMS. By identifying patients with varying deletion sizes, these data will aid die construction of a long-range deletion-based map of 17p11.2 and identification of the genes involved in this syndrome.