Cat eye syndrome chromosome breakpoint clustering: identification of two intervals also associated with 22q11 deletion syndrome breakpoints

Abstract

The supernumerary cat eye syndrome (CES) chromosome is dicentric, containing two copies of 22pter→q11.2. We have found that the duplication breakpoints are clustered in two intervals. The more proximal, most common interval is the 450–650 kb region between D22S427 and D22S36, which corresponds to the proximal deletion breakpoint interval found in the 22q11 deletion syndrome (DiGeorge/velocardiofacial syndrome). The more distal duplication breakpoint interval falls between CRKL and D22S112, which overlaps with the common distal deletion interval of the 22q11 deletion syndrome. We have therefore classified CES chromosomes into two types based on the location of the two breakpoints required to generate them. The smaller type I CES chromosomes are symmetrical, with both breakpoints located within the proximal interval. The larger type II CES chromosomes are either asymmetrical, with one breakpoint located in each of the two intervals, or symmetrical, with both breakpoints located in the distal interval. The co-localization of the breakpoints of these different syndromes, plus the presence of low-copy repeats adjacent to each interval, suggests the existence of several specific regions of chromosomal instability in 22q11.2 which are involved in the production of both deletions and duplications. Since the phenotype associated with the larger duplication does not appear to be more severe than that of the smaller duplication, determination of the type of CES chromosome does not currently have prognostic value.

Interstitial 22q13 deletions: genes other than SHANK3 have major effects on cognitive and language development

“…The DNA was isolated using QIAGEN s Maxi Kit and was labeled using GIBCOBRL s BioNick Labeling system. The biotinylated probes were detected using the protocol of McTaggart et al, 17 with FITC-avidin and antiavidin purchased from Vector Laboratories.…”

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

“…11 A small (type I) CES chromosome 17 was detected in 50% of the cells in an AC. The boy reportedly had mild CES at the age of 1.5 years.…”

“…DNAs of cosmids, BACs, and YACs (Tables 1 and 2) were amplified and labeled as described in previous studies. 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).…”

“…However, as shown here and elsewhere, a subset of cases may require additional probes. 7,11,17 The stepwise investigation of minute SMCs (classes III and IV) included (i) the identification of the a-satellite suprachromosomal family by low-stringency hybridization allowing cross-hybridization between members of the same suprafamily, 13 (ii) the identification of the chromosomal origin by highstringency (chromosome-specific) hybridization of alphoid DNA probes, and (iii) analysis of the euchromatin DNA content using region-specific probes such as BACs. 7,11 There have been attempts to detect the euchromatin on SMCs by using of whole chromosome painting, 16 but due to the presence of centromeric DNA in some paints, this approach is artifact prone: heterochromatic and euchromatic SMCs (classes I vs II or classes III vs IV) may be confused.…”

“…The de novo cases included a small ring chromosome (case 9), an atypical CES chromosome (case 36), 11 and three typical CES chromosomes (cases 22, 33, and 40). 17 There has been no previous report on the prevalence of SMCs conferring extra copies of the CECR at prenatal diagnosis. For the CES, a frequency between 1:50 000 and 1:150 000 was estimated from patients observed in Switzerland (OMIM 115470).…”