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

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

Author Guilherme, R. S. Autor UNIFESP Google Scholar
Cernach, M. C. S. P. Autor UNIFESP Google Scholar
Sfakianakis, T. E. Autor UNIFESP Google Scholar
Takeno, S. S. Autor UNIFESP Google Scholar
Nardozza, L. M. M. Autor UNIFESP Google Scholar
Rossi, C. Autor UNIFESP Google Scholar
Bhatt, S. S. Google Scholar
Liehr, T. Google Scholar
Melaragno, M. I. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Jena
Abstract 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
Keywords Complex chromosomal rearrangement
CCR
FISH
Genomic imbalance
SNP array
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Else Kroner-Fresenius-Stiftung
Grant number FAPESP: 10/50737-1
CAPES: 2333-11-2
Else Kroner-Fresenius-Stiftung: 2011_A42
Date 2013-01-01
Published in Cytogenetic and Genome Research. Basel: Karger, v. 141, n. 4, p. 317-323, 2013.
ISSN 1424-8581 (Sherpa/Romeo, impact factor)
Publisher Karger
Extent 317-323
Origin http://dx.doi.org/10.1159/000353302
Access rights Closed access
Type Article
Web of Science ID WOS:000326436700008
URI http://repositorio.unifesp.br/handle/11600/35850

Show full item record




File

File Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Search


Browse

Statistics

My Account