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

Abstract

Supernumerary marker chromosomes (SMCs) are frequently found at pre-and postnatal cytogenetic diagnosis and require identification. A disproportionally large subset of SMCs is derived from the human chromosome 22 and confers tri-or tetrasomy for the cat eye chromosomal region (CECR, the proximal 2 Mb of chromosome 22q) and/or other segments of 22q. Using fluorescence in situ hybridization (FISH) and 15 different DNA probes, we studied nine unrelated patients with an SMC(22) that contained the CECR. Five patients showed the small (type I) cat eye syndrome (CES) chromosome and each one had the larger (type II) CES chromosome, small ring chromosome 22, der(22)t(11;22) extrachromosome, and a novel type of bisatellited SMC (22) with breakpoints outside the low-copy repeats (LCRs22). By size and morphology, the novel bisatellited SMC(22) resembled the typical (types I and II) CES chromosomes, but it might have been associated with the chromosome 22q duplication syndrome, not CES. This SMC included a marker from band 22q12.3 and conferred only one extra copy each of the 22 centromere, CECR, and common 22q11 deletion area. There has been no previous report of a bisatellited SMC(22) predicting the chromosome 22q duplication syndrome. Accounting for the cytogenetic resemblance to CES chromosomes but different makeup and prognosis, we propose naming this an atypical (type III) CES chromosome. In this study, we found six distinct intervals on 22q to be relevant for FISH diagnostics. We propose to characterize SMCs(22) using DNA probes corresponding to these intervals.

Forty-two supernumerary marker chromosomes (SMCs) in 43 273 prenatal samples: chromosomal distribution, clinical findings, and UPD studies

“…The affected twin had severe malformations and died on day one of life. 11 The cotwin had no anomalies.…”

“…11 The SMC (Figure 1) was present in 19% of the cells of an AC performed at 14 þ 6 weeks of gestation and in 3% of cells after FBS. It revealed a trisomy of 22p11 -q13.…”

“…14,15 SMCs(22) were analyzed using cosmid cos121 16 and, following the report of McTaggart et al, 17 additional BAC clones (Tables 1 and 2). 11 Slides were counterstained with DAPI and analyzed using Axioskopt epifluorescence microscopes (Carl Zeiss, Göttingen, Germany) and the ISISt imaging system (MetaSystems, Altlussheim, Germany). At least six informative metaphases were scored for each probe.…”

“…11 An AC was performed at 14 þ 5 weeks of gestation. G banding ( Figure 1) and FISH ( Figure 2) showed a large (type II) CES SMC present in all cells.…”

“…11 In a twin pregnancy, an AC was performed at 15 weeks of gestation. An SMC was detected and using FISH, a der(22)t(11;22) extrachromosome was identified.…”