DNA FLUORESCENT-PROBES FOR DIAGNOSIS OF VELOCARDIOFACIAL AND RELATED SYNDROMES

Objective: To study the usefulness of fluorescent in situ hybridizatio n (FISH) with the DNA probe D22S75 for detecting microdeletions in chr omosome 22q11.2 in metaphases from patients with features of ''CATCH 2 2'' (cardiac anomalies, abnormal facies, thymic hypoplasia or aplasia, cleft palate, and hypocalcemia). Methods: High-resolution chromosome analysis and FISH were performed on metaphases from 10 control subject s, 42 patients with features of CATCH 22, and 6 parents of children wi th CATCH 22, Patients were screened for conotruncal heart defect, pala tal abnormality, and facial features, We correlated the phenotype, kar yotype, and deletion of a D22S75 locus. Results: Specimens from nine p atients with one or more features of CATCH 22 had a single hybridizati on signal for D22S75, indicating a deletion of chromosome 22q11.2. Fou r patients had ail the major features of the syndrome and a chromosoma l deletion, Thirteen patients had two CATCH 22 features, five of whom had a deletion, None of the 25 patients with a single CATCH 22 feature had a deletion, One patient with a deletion detected by FISH also had a deletion noted on high-resolution banding, All six parents who had blood samples studied by FISH had normal hybridization patterns, Concl usion: FISH is a useful adjunct to chromosome analysis for assessing p atients with features of CATCH 22, Detecting a chromosomal deletion by FISH provides a definitive diagnosis and helps to ensure appropriate medical management and genetic counseling.