Article

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

ABSTRACT

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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    • "Inheritance for detected CNVs was determined by visualizing a child and his parents' results side by side in the software, assigning an inherited status to a child's CNV call if there was ≥ 80% overlap with a parental CNV call. Since microarray analysis alone does not allow chromosomal position analysis of the detected CNVs, apparently de novo CNVs could in fact be inherited from a parent through an insertional translocation, although these rearrangements are rare events (incidence of insertional translocations detected by microarrays was estimated at 1:3380 to 1:5200 in the general population by Neill et al. [28] and 1 in 500 individuals referred for clinical CGH analysis by Kang et al. [29]). Because we are interested in the copy number state, which in that case would indeed be de novo, and for conciseness purposes, we will refer to all apparently de novo CNVs as " de novo CNVs " . "
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