A cryptic deletion of 2q35 including part of the PAX3 gene detected by breakpoint mapping in a child with autism and a de novo 2;8 translocation

Borg, Isabella; Squire, Michael; Menzel, Corinna; Stout, K.; Morgan, David L.; Willatt, Lionel; O’Brien, Peter C.; Ferguson‐Smith, Malcolm A.; Ropers, Hans Hilger; Tommerup, Niels; Kalscheuer, Vera M.; Sargan, David R.

doi:10.1136/jmg.39.6.391

Cited by 41 publications

(37 citation statements)

References 28 publications

(14 reference statements)

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“…These aberrations were collectively called "cryptic" because it was not possible to detect them before with the light microscope (de Vries et al, 2001;Fan et al, 2001;Riegel et al, 2001;Anderlid et al, 2002;Baker et al, 2002). Also, an obscure syndrome like autism is apparently related to subtelomeric aberrations (Borg et al, 2002;Wolff et al, 2002;Keller et al, 2003).…”

confidence: 99%

Cytological indications of the complex subtelomeric structure

2004

Cytogenet Genome Res

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Research on the subtelomeric region has considerably increased because this chromosome segment (1) keeps the chromosome number constant, (2) intervenes in cancer and cell senescence processes, (3) presents more crossovers than other regions of the genome and, (4) is the site of cryptic chromosome aberrations associated with mental retardation and congenital malformations. Quantitative microphotometrical scanning and computer graphic image analysis enables the detection of differentially distributed Giemsa-stained structures in T-banded subtelomeric segments of human and Chinese hamster ovary (CHO) chromosomes. The presence of high density stain patterns in the subtelomeric region was confirmed using endoreduplicated chromosomes as a model. Besides, prolonging the incubation in the T-buffer, specific holes were induced in subtelomeric segments. Hole specificity was confirmed inducing them in complex CHO chromosome aberrations obtained by AluI. The method was also used to detect minute sister chromatid exchanges in the T-banded subtelomeric area (t-SCEs). The presence of t-SCEs was suspected to reflect, at the microscope level, the high crossover activity prevailing in the region. Due to the fact that the fluorescent signals obtained with subtelomeric probes seem to be colocalized with subtelomeric high density areas, measurements on the position of both structures with respect to the diffraction and chromosome edges were carried out. Data obtained showed comparable values suggesting that the high density segments were located where telomeric probes usually fluoresce. The possible relationship of the high density patterns, the production of specific holes, the localization of fluorescent areas and the detection of minute SCEs in the subtelomeric segment observed in T-banded CHO and human chromosomes is briefly reviewed.

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confidence: 99%

Cytological indications of the complex subtelomeric structure

2004

Cytogenet Genome Res

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“…An increasing number of apparently "balanced" de novo chromosomal rearrangements have been associated with phenotypic abnormalities in recent years. [3][4][5] A number of hypotheses have been postulated as to the cause of the phenotypic abnormalities. These include (1) a cryptic deletion undetected cytogenetically, causing the loss of a gene or genes, 6,7 (2) a break in a gene at the translocation or inversion breakpoint, leading to loss of function, 8 -10 (3) position effects due to the new cytogenetic rearrangement, 11,12 or (4) uniparental disomy, particularly in chromosomes known to be affected by imprinting.…”

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confidence: 99%

Detection of deletions in de novo “balanced” chromosome rearrangements: Further evidence for their role in phenotypic abnormalities

Astbury

Christ

Aughton

et al. 2004

Genetics in Medicine

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Purpose: The purpose of this study was to test the hypothesis that deletions of varying sizes in de novo apparently balanced chromosome rearrangements are a significant cause of phenotypic abnormalities. Methods: A total of fifteen patients, with seemingly balanced de novo rearrangements by routine cytogenetic analysis but with phenotypic anomalies, were systematically analyzed. We characterized the breakpoints in these fifteen cases (two of which were ascertained prenatally), using a combination of high-resolution GTG-banding, fluorescence in situ hybridization (FISH) with bacterial artificial chromosomes (BACs), and data from the Human Genome Project.Results: Molecular cytogenetic characterization of the 15 patients revealed nine with deletions, ranging in size from 0.8 to 15.3 Mb, with the number of genes lost ranging from 15 to 70. In five of the other six cases, a known or putative gene(s) was potentially disrupted as a result of the chromosomal rearrangement. In the remaining case, no deletions were detected, and no known genes were apparently disrupted. Conclusions: Our study suggests that the use of molecular cytogenetic techniques is a highly effective way of systematically delineating chromosomal breakpoints, and that the presence of deletions of varying size is an important cause of phenotypic abnormalities in patients with "balanced" de novo rearrangements. Genet Med 2004:6(2):81-89.

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“…Several studies reveal that 'apparently' balanced reciprocal translocations are associated with cryptic small deletions or duplications at the breakpoints or on other chromosomes (Borg et al, 2002;Cox et al, 2003;Gribble et al, 2005). Therefore, we suggest to first analyze gDNA of this patient by array CGH in order to exclude 'cryptic' deletions or duplications at the breakpoints or on other chromosomes.…”

Section: Discussionmentioning

confidence: 99%

Array painting using microdissected chromosomes to map chromosomal breakpoints

Backx¹,

Esch²,

Melotte³

et al. 2007

Cytogenet Genome Res

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Molecular characterization of breakpoints of chromosomal rearrangements is a successful strategy for the identification of candidate disease genes. Mapping translocation breakpoints and rearranged chromosomal boundaries is labor intensive and/or time consuming. Here, we present a novel and rapid procedure to map such chromosomal breakpoints by hybridizing amplified microdissection derived DNA of aberrant chromosomes to arrays containing genomic clones. We illustrate the potential of the technique by molecularly delineating the breakpoints in five small supernumerary marker chromosomes (sSMC) and mapping the breakpoints of five different chromosomal translocations.

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A cryptic deletion of 2q35 including part of the PAX3 gene detected by breakpoint mapping in a child with autism and a de novo 2;8 translocation

Cited by 41 publications

References 28 publications

Cytological indications of the complex subtelomeric structure

Cytological indications of the complex subtelomeric structure

Detection of deletions in de novo “balanced” chromosome rearrangements: Further evidence for their role in phenotypic abnormalities

Array painting using microdissected chromosomes to map chromosomal breakpoints

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