Use of fluorescence in situ hybridization (FISH) in the diagnosis of DiGeorge sequence and related diseases.

The proximal portion of human chromosome 22q has been implicated in the pathogenesis of a clinically diverse group of conditions including DiGeorge sequence (DGS), velocardiofacial syndrome, and CHARGE association as well as isolated conotruncal heart anomalies. Frequently, overlap in the clinical presentation of these syndromes occurs and, recently, the presence of microdeletions on chromosome 22q11.2 with varying frequencies has been demonstrated in these syndromes. Using fluorescence in situ hybridization (FISH), we assessed 20 consecutive patients who were cytogenetically and clinically evaluated for a suspected syndrome that could be due to a microdeletion of chromosome 22q11.2. After cytogenetic testing and full clinical evaluation, we compared the results by FISH with the final clinical diagnosis and karyotype results. We found that microdeletions of 22q11.2 were detected in three of the five patients who were evaluated for DGS. The three cases with microdeletions appeared clinically to have DGS while the two negative cases were more atypical. High-resolution banding techniques did not detect a microdeletion in any of the cases; however, one of the 20 patients had a translocation between chromosomes 13 and 22. This patient also had a microdeletion of 22q11.2 detected by FISH and clinical features of DGS. None of the patients who were evaluated for disorders related to DGS showed microdeletions. We conclude that FISH is a useful, easily applied technique for the diagnosis of 22q11.2 microdeletion syndromes, particularly DGS. This test may also be useful in genetic counseling and in both prenatal and postnatal diagnoses.