DiGeorge/velocardiofacial syndrome: FISH studies of chromosomes 22q11 and 10p14, and clinical reports on the proximal 22q11 deletion

Abstract

DiGeorge anomaly/velocardiofacial syndrome (DG/VCFS) occurs with different deletion intervals on chromosomes 22q11, while the DiGeorge anomaly (with other findings) is seen in patients with deletions of 10p14. The clinical outcome with the common 22q11 deletion (90% of cases) is well known, but the outcome with the less frequent deletion types has not been well documented. Using cytogenetic and fluorescence in situ hybridization (FISH) analysis we studied a series of 295 patients with suspected DG/VCFS. We identified 58 subjects with a 22q11 deletion, and none with a 10p deletion. Fifty-two subjects had the common deletion, five had the proximal deletion, and one had an atypical proximal deletion due to a 1;22 translocation. We report clinical data of four subjects with the proximal 22q11 microdeletion, and of one patient with the atypical proximal deletion. The anomalies observed with the proximal 22q11 microdeletion fell within the DG/VCFS spectrum. Two females, 6 and 25 years old, had normal mental development. Normal development has been reported with the common 22q11 deletion, but only in a minority of cases. This study may indicate a better intellectual and/or behavioral outcome with the proximal vs. the common 22q11 deletion, rather than a chance finding.

FISH of supernumerary marker chromosomes (SMCs) identifies six diagnostically relevant intervals on chromosome 22q and a novel type of bisatellited SMC(22)

“…The breakpoint area of the constitutional 11;22 translocation differs from the typical CES breakpoints and corresponds with the nested distal breakpoints of the proximal 22q11 deletion, which is present in about 10% of patients with DG/VCFS. 19,24,31 Here, we found the BACs 201C11 and 919E7 (interval 3) present on the der(22)t (11;22) extrachromosome. This finding is in line with results from the proximal 22q11 deletion 19 and a position of the t(11;22) breakpoint area at the LCR-B 25 or LCR22-4.…”

“…19,24,31 Here, we found the BACs 201C11 and 919E7 (interval 3) present on the der(22)t (11;22) extrachromosome. This finding is in line with results from the proximal 22q11 deletion 19 and a position of the t(11;22) breakpoint area at the LCR-B 25 or LCR22-4. 26 BACs 217D6, 966B6, 256C5, 384D8, and 799F10 (intervals 5 and 6) defined the segment of 22q that is lacking on type II CES chromosomes.…”

“…These BACs map to the middle section of band 22q11.21 and define the type II CES SMC area, also known as the interval of the common 22q11 deletion. 9,19,23,24 The breakpoint of the constitutional 11;22 translocation (patient 9) was located within this cluster in between BACs 919E7 (present on the der (22)) and 219G6 (absent from the der (22)). This breakpoint colocalized with the distal breakpoint area of the proximal 22q11 deletion.…”

“…This breakpoint colocalized with the distal breakpoint area of the proximal 22q11 deletion. 19 (5) BACs 217D6, 966B6, and 256C5 hybridized only to the unusual bisatellited SMC (Figure 1) of patient 7 and to the ring-like SMC(22) of patient 8. (6) The most distal clones, 384D8 and 799F10, were absent from all SMCs in this study.…”

“…21 Table 2 provides properties of the probes and the order of location from 22pter. After preselecting 20 BACs from the CTA library based on their size and location on the human chromosome 22q 21 and testing each clone using FISH on 25 normal controls, we selected 12 BACs (including the previously described clones 678G6, 201C11, 219G6, 384D8, and 799F10) 19,20 that showed clear FISH signals, no variation of hybridization at normal 22s, and no second sites at other chromosomes. Cosmid/BAC DNA was amplified using a degenerate oligonucleotide primed shuttle polymerase chain reaction (DOP-shuttle-PCR) protocol.…”