Characterization of the Supernumerary Chromosome in Cat Eye Syndrome

McDermid, Heather E.; Duncan, Alessandra M.V.; Brasch, Klaus; Holden, J. J. A.; Magenis, Ellen; Sheehy, Robert; Burn, John; Kardon, Nataline; Noël, Bernard; Schinzel, Albert; Teshima, Ikuko; White, Bradley N.

doi:10.1126/science.3961499

Cited by 147 publications

(54 citation statements)

References 5 publications

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“…In these studies, the level of mosaicism overall was reported to range from 13 to 50% (ave. 46%), but with B30% of the acrocentric SMCs compared with B70% of the nonacrocentric SMCs being classified as mosaics. 2,4,10,22,23 Further analyses of our data show that within the acrocentric SMCs, 20% of the SMC(15) and SMC (22) were mosaic compared with 31% for SMC (14) and 50% for SMC(13/21) respectively. Previous reports on SMC(15) have shown that on average B85% of SMC(15)s present as nonmosaics 13,24,28 and the majority of SMC (22) reported are also nonmosaics.…”

Section: Mosaicism and The Chromosomal Origins Of Smcsmentioning

confidence: 99%

Supernumerary marker chromosomes in man: parental origin, mosaicism and maternal age revisited

et al. 2004

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The details of all cytogenetic abnormalities diagnosed in the Wessex Regional Genetics Laboratory (WRGL) since 1967 to the present day have been recorded in the Salisbury Treasury of Interesting Chromosomes (STOIC). From this resource, we identified 137 patients with constitutional autosomal supernumerary marker chromosomes (SMC) ascertained in four principal groups: (i) 37% with abnormal phenotypes; (ii) 7% couples with reproductive difficulties; (iii) 47% antenatal diagnoses and (iv) 9% miscellaneous. Overall, 81 (59%) SMCs were mosaics and 56 (41%) nonmosaics. Of the 109 cases with known parental origins, 70% were de novo, 19% maternally and 11% paternally inherited. The chromosomal origins of 112/137 (82%) of the SMCs have been determined by fluorescence in situ hybridization (FISH). In all, 36/112 (32%) were derived from nonacrocentric autosomes, and 76/112 (68%) from the acrocentric autosomes 13/21, 14, 15 and 22. Of these acrocentric SMCs, 39 (51%) were derived from chromosome 15, so that SMC(15) constituted 39/112 (35%) of all SMCs with known chromosomal origins. The frequencies with which mosaicism was observed varied considerably according to the chromosomal origin of the SMCs and accounted for 8/39 (20%) SMC(15), 13/37 (35%) SMCs from other acrocentrics and 25/36 (69%) of nonacrocentric SMCs. The data were analysed for parental age effects, and only de novo SMC(15)s were found to be associated with a significantly increased maternal age.

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Section: Mosaicism and The Chromosomal Origins Of Smcsmentioning

confidence: 99%

Supernumerary marker chromosomes in man: parental origin, mosaicism and maternal age revisited

et al. 2004

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“…Further, the breakpoints implicated in generating the cat eye chromosome, a supernumerary inverted duplication of proximal 22q implicated in cat eye syndrome (CES; MIM# 115470), frequently match the proximal LCR or one of the more distal LCRs of the 22q11.2 region [McDermid et al, 1986;Mears et al, 1994]. However, detailed analysis of the extent of the duplicated material and its relationship to the ensuing phenotype has been minimal.…”

Section: Introductionmentioning

confidence: 99%

Detailed analysis of 22q11.2 with a high density MLPA probe set

et al. 2008

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The presence of chromosome-specific low-copy repeats (LCRs) predisposes chromosome 22 to deletions and duplications. The current diagnostic procedure for detecting aberrations at 22q11.2 is chromosomal analysis coupled with fluorescence in situ hybridization (FISH) or PCR-based multiplex ligation dependent probe amplification (MLPA). However, there are copy number variations (CNVs) in 22q11.2 that are only detected by high-resolution platforms such as array comparative genomic hybridization (aCGH). We report on development of a high-definition MLPA (MLPA-HD) 22q11 kit that detects copy number changes at 37 loci on the long arm of chromosome 22. These include the 3-Mb region commonly deleted in DiGeorge/velocardiofacial syndrome (DGS/ VCFS), the cat eye syndrome (CES) region, and more distal regions in 22q11 that have recently been shown to be deleted. We have used this MLPA-HD probe set to analyze 363 previously wellcharacterized samples with a variety of different rearrangements at 22q11 and demonstrate that it can detect copy number alterations with high sensitivity and specificity. In addition to detection of the common recurrent deletions associated with DGS/VCFS, variant and novel chromosome 22 aberrations have been detected. These include duplications within as well as deletions distal to this region. Further, the MLPA-HD detects deletion endpoint differences between patients with the common 3-Mb deletion. The MLPA-HD kit is proposed as a cost effective alternative to the currently available detection methods for individuals with features of the 22q11 aberrations. In patients with the relevant phenotypic characteristics, this MLPA-HD probe set could replace FISH for the clinical diagnosis of 22q11.2 deletions and duplications.

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“…Parental follow-up was not possible for this case. However, because Cat Eye syndrome is caused by a duplication of the proximal region of 22q11, which is usually observed as an additional marker chromosome, 29,30 but can also be seen as an interstitial duplication, 31-33 the 22q11 duplication detected by the array is likely to be related to this individual's phenotype. It also demonstrates that a microarray containing all clinically important target loci is useful for postnatal screening assays.…”

Section: Polymorphismsmentioning

confidence: 99%

Detection and calibration of microdeletions and microduplications by array-based comparative genomic hybridization and its applicability to clinical genetic testing

Wong¹,

Martin²,

Heretis³

et al. 2005

Genetics in Medicine

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Purpose: Genome-wide telomere screening by fluorescence in situ hybridization (FISH) has revealed that Ϸ 6% of unexplained mental retardation is due to submicroscopic telomere imbalances. However, the use of FISH for telomere screening is labor intensive and time consuming, given that 41 telomeres are interrogated. We have evaluated the use of array-based Comparative Genomic Hybridization (aCGH) as a more efficient tool for identifying telomere rearrangements. Methods: In this study, 102 individuals with unexplained mental retardation, with either normal or abnormal FISH results, were selected for a blinded retrospective study using aCGH. Results between the two methodologies were compared to ascertain the ability of aCGH to be used in a clinical diagnostics setting. Results:We detected 100% of all imbalances previously identified by FISH (n ϭ 17) and identified two additional abnormalities, a 10q telomere duplication and an interstitial duplication of 22q11. Interphase FISH analysis verified all abnormal array results. We also demonstrated that aCGH can accurately calibrate the size of telomere imbalances by using an array with "molecular rulers" for the telomeric regions of 1p, 16p, 17p, and 22q.Conclusion: This study demonstrates that aCGH is an equivalent methodology to telomere FISH for detecting submicroscopic deletions. In addition, small duplications that are not easily visible by FISH can be accurately detected using aCGH. Because aCGH allows simultaneous interrogation of hundreds to thousands of DNA probes and is more amenable to automation, it offers an efficient and high-throughput alternative for detecting and calibrating unbalanced rearrangements, both of the telomere region, as well as other genomic locations. Genet Med 2005:7(4):264 -271.

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Characterization of the Supernumerary Chromosome in Cat Eye Syndrome

Cited by 147 publications

References 5 publications

Supernumerary marker chromosomes in man: parental origin, mosaicism and maternal age revisited

Supernumerary marker chromosomes in man: parental origin, mosaicism and maternal age revisited

Detailed analysis of 22q11.2 with a high density MLPA probe set

Detection and calibration of microdeletions and microduplications by array-based comparative genomic hybridization and its applicability to clinical genetic testing

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