Dual-probe fluorescence in situ hybridization assay for detecting deletions associated with VCFS/DiGeorge syndrome I and DiGeorge syndrome II loci

Over 90% of patients with DiGeorge syndrome (DGS) or velocardiofacial syndr ome (VCFS) have a microdeletion at 22q11.2. Given that these deletions are difficult to visualize at the light microscopic level, fluorescence in situ hybridization (FISH) has been instrumental in the diagnosis of this disord er. Deletions on the short arm of chromosome 10 are also associated with a DGS-like phenotype, Since deletions at 22q11.2 and at 10p13p14 result in si milar findings, we have developed a dual-probe FISH assay for screening sam ples referred for DGS or VCFS in the clinical laboratory. This assay includ es two test probes for the loci, DGSI at 22q11.2 and DGSII at 10p13p14, and centromeric probes for chromosomes 10 and 22, Of 412 patients tested, 54 w ere found to be deleted for the DG;SI locus on chromosome 22 (13%), and a s ingle patient was found deleted for the DGSII locus on chromosome 10 (0.24% ), The patient with the 10p deletion had facial features consistent with VC FS, plus sensorineural hearing loss, and renal anomalies. Cytogenetic analy sis showed a large deletion of 10p [46,XX,del(10)(p12.2p14)] and FISH using a 10p telomere region-specific probe confirmed the interstitial nature of the deletion. Analysis for the DGSI and the DGSII loci suggests that the de letion of the DGSII locus on chromosome 10 may be 50 times less frequent th an the deletion of DGSI on chromosome 22, The incidence of deletions at 22q 11.2 has been estimated to be 1 in 4000 newborns; therefore, the deletion a t 10p13p14 may be estimated to occur in 1 in 200,000 live births. (C) 2000 Wiley-Liss, Inc.