SIMULTANEOUS, MULTILOCUS FISH ANALYSIS FOR DETECTION OF MICRODELETIONS IN THE DIAGNOSTIC EVALUATION OF DEVELOPMENTAL DELAY AND MENTAL-RETARDATION

Many microdeletion and contiguous gene-deletion syndromes include ment al retardation as a clinical feature. We have developed MultiFISH, a F ISH assay using several probes to simultaneously screen for multiple m icrodeletion syndromes in patients who present with unexplained develo pmental delay and/or mental retardation. This screening tool can be us ed to determine whether a particular microdeletion syndrome is involve d in the etiology of these clinical phenotypes. In this pilot study we combined probes for the commonly deleted regions of Prader-Willi, Ang elman, Williams, Smith-Magenis, and DiGeorge/velocardiofacial syndrome s in a single hybridization. The probes were differentially labeled, a llowing multicolor detection, and 200 individual samples were screened in a blinded fashion. For all patients found by MultiFISH to have del etions, the deletions were originally identified and/or later confirme d by use of single-probe FISH analysis in our diagnostic cytogenetics laboratory. One patient, who was referred for developmental delay and was shown to have a normal G-banded karyotype, was identified by Multi FISH as having a microdeletion at the DiGeorge/velocardiofacial common ly deleted region. Forty-six of the 200 total samples were tested for microdeletions by use of single FISH probes in the diagnostic laborato ry. Ten of these cases were found to have deletions, and all deletions were subsequently detected by use of a MultiFISH screen performed in a blinded fashion. Additionally, for all 200 patients tested by use of MultiFISH, no false-positive deletion results were observed. We demon strate the ability of this technique to scan for and to identify micro deletions in a proportion of patients whose routine karyotype appears normal yet who are mentally retarded and/or developmentally delayed.