Insertional Translocation Detected Using FISH Confirmation of Array-Comparative Genomic Hybridization (aCGH) Results

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 05/2010; 152A(5):1111-26. DOI: 10.1002/ajmg.a.33278
Source: PubMed


Insertional translocations (ITs) are rare events that require at least three breaks in the chromosomes involved and thus qualify as complex chromosomal rearrangements (CCR). In the current study, we identified 40 ITs from approximately 18,000 clinical cases (1:500) using array-comparative genomic hybridization (aCGH) in conjunction with fluorescence in situ hybridization (FISH) confirmation of the aCGH findings, and parental follow-up studies. Both submicroscopic and microscopically visible IT events were detected. They were divided into three major categories: (1) simple intrachromosomal and interchromosomal IT resulting in pure segmental trisomy, (2) complex IT involving more than one abnormality, (3) deletion inherited from a parent with a balanced IT resulting in pure segmental monosomy. Of the cases in which follow-up parental studies were available, over half showed inheritance from an apparently unaffected parent carrying the same unbalanced rearrangement detected in the propositi, thus decreasing the likelihood that these IT events are clinically relevant. Nevertheless, we identified six cases in which small submicroscopic events were detected involving known disease-associated genes/genomic segments and are likely to be pathogenic. We recommend that copy number gains detected by clinical aCGH analysis should be confirmed using FISH analysis whenever possible in order to determine the physical location of the duplicated segment. We hypothesize that the increased use of aCGH in the clinic will demonstrate that IT occurs more frequently than previously considered but can identify genomic rearrangements with unclear clinical significance.

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Available from: Sau Wai Cheung, Dec 11, 2014
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    • "These unbalanced insertions have been detected by fluorescence in situ hybridization to differentiate between tandem duplications and non-recurrent insertions [Kang et al., 2010; Neill et al., 2011]. Identical unbalanced rearrangements have also been identified in phenotypically normal parents and affected probands [Kang et al., 2010; Neill et al., 2011], suggesting that additional confounding factors, as mentioned above, determine the phenotypic outcome of an inherited unbalanced insertion similar to tandem duplication. We identified tandem duplication in the patient and his father and excluded the possibility that the phenotype of the patient was caused by disruption or dysregulation of a gene at a different location in the genome. "
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    • "Comparing the clinical data of our patients with the data reported by Zollino et al. [5] in patients with classical WHS phenotype and deletions between 5 and 18 Mb (Table 1), the only major differences were the absence of ocular coloboma and hypospadias. Until now, few WHS patients had been studied by genomic high-resolution methods [1, 2, 4, 10, 14, 20]. As the number of these studies increases, a better determination of the exact size of deletions will be achieved, improving the definition of the regions and genes implicated in each phenotypic trait associated with the classical WHS. "
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    • "Unbalanced IT events can result in abnormal phenotype by increased or decreased expression of genes located in duplicated or deleted segments, respectively. Alternatively, abnormal gene expression may result from position effect due to deletions, duplications or repositioning in flanking regions of genes [Kang et al., 2010]. "
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