DNA fluorescent probes for diagnosis of velocardiofacial and related syndromes

To study the usefulness of fluorescent in situ hybridization (FISH) with the DNA probe D22S75 for detecting microdeletions in chromosome 22q11.2 in metaphases from patients with features of "CATCH 22" (cardiac anomalies, abnormal facies, thymic hypoplasia or aplasia, cleft palate, and hypocalcemia).

High-resolution chromosome analysis and FISH were performed on metaphases from 10 control subjects, 42 patients with features of CATCH 22, and 6 parents of children with CATCH 22. Patients were screened for conotruncal heart defect, palatal abnormality, and facial features. We correlated the phenotype, karyotype, and deletion of a D22S75 locus.

Specimens from nine patients with one or more features of CATCH 22 had a single hybridization signal for D22S75, indicating a deletion of chromosome 22q11.2. Four patients had all the major features of the syndrome and a chromosomal 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.

FISH is a useful adjunct to chromosome analysis for assessing patients 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.