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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A Complex Chromosome Rearrangement Involving Four Chromosomes, Nine Breakpoints and a Cryptic 0.6-Mb Deletion in a Boy with Cerebellar Hypoplasia and Defects in Skull Ossification

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Guilherme, R. S. [1] ; Cernach, M. C. S. P. [1] ; Sfakianakis, T. E. [1] ; Takeno, S. S. [1] ; Nardozza, L. M. M. [2] ; Rossi, C. [3] ; Bhatt, S. S. [4] ; Liehr, T. [4] ; Melaragno, M. I. [1]
Total Authors: 9
[1] Univ Fed Sao Paulo, Dept Morphol & Genet, Div Genet, BR-04023900 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Obstet, Fetal Med Div, BR-04023900 Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Neonatal Pediat Div, BR-04023900 Sao Paulo - Brazil
[4] Univ Jena, Jena Univ Hosp, Inst Human Genet, Jena - Germany
Total Affiliations: 4
Document type: Journal article
Source: Cytogenetic and Genome Research; v. 141, n. 4, p. 317-323, 2013.
Web of Science Citations: 4

Constitutional complex chromosomal rearrangements (CCRs) are considered rare cytogenetic events. Most apparently balanced CCRs are de novo and are usually found in patients with abnormal phenotypes. High-resolution techniques are unveiling genomic imbalances in a great percentage of these cases. In this paper, we report a patient with growth and developmental delay, dysmorphic features, nervous system anomalies (pachygyria, hypoplasia of the corpus callosum and cerebellum), a marked reduction in the ossification of the cranial vault, skull base sclerosis, and cardiopathy who presents a CCR with 9 breakpoints involving 4 chromosomes (3, 6, 8 and 14) and a 0.6-Mb deletion in 14q24.1. Although the only genomic imbalance revealed by the array technique was a deletion, the clinical phenotype of the patient most likely cannot be attributed exclusively to haploinsufficiency. Other events must also be considered, including the disruption of critical genes and position effects. A combination of several different investigative approaches (G-banding, FISH with different probes and SNP array techniques) was required to describe this CCR in full, suggesting that CCRs may be more frequent than initially thought. Additionally, we propose that a chain chromosome breakage mechanism may have occurred as a single rearrangement event resulting in this CCR. This study demonstrates the importance of applying different cytogenetic and molecular techniques to detect subtle rearrangements and to delineate the rearrangements at a more accurate level, providing a better understanding of the mechanisms involved in CCR formation and a better correlation with phenotype. Copyright (C) 2013 S. Karger AG, Basel (AU)