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Gijsbers, A.C.J.; Bosch, C.A.J.; Dauwerse, J.G.; Giromus, O.; Hansson, K.; Hilhorst-Hofstee, Y.; ... ; Ruivenkamp, C.A.L. (2010)

Additional cryptic CNVs in mentally retarded patients with apparently balanced karyotypes

Article / Letter to editor
Apparently balanced chromosome abnormalities are occasionally associated with mental retardation (MR). These balanced rearrangements may disrupt genes. However, the phenotype may also be caused by small abnormalities present at the breakpoints or elsewhere in the genome. Conventional karyotyping is not instrumental for detecting small abnormalities because it only identifies genomic imbalances larger than 5-10 Mb. In contrast, high-resolution whole-genome arrays enable the detection of submicroscopic abnormalities in patients with apparently balanced rearrangements. Here, we report on the whole-genome analysis of 13 MR patients with previously detected balanced chromosomal abnormalities, five de novo, four inherited, and four of unknown inheritance, using Single Nucleotide Polymorphism (SNP) arrays. In all the cases, the patient had an abnormal phenotype. In one familial case and one unknown inheritance case, one of the parents had a phenotype which appeared identical to the patient...Show moreApparently balanced chromosome abnormalities are occasionally associated with mental retardation (MR). These balanced rearrangements may disrupt genes. However, the phenotype may also be caused by small abnormalities present at the breakpoints or elsewhere in the genome. Conventional karyotyping is not instrumental for detecting small abnormalities because it only identifies genomic imbalances larger than 5-10 Mb. In contrast, high-resolution whole-genome arrays enable the detection of submicroscopic abnormalities in patients with apparently balanced rearrangements. Here, we report on the whole-genome analysis of 13 MR patients with previously detected balanced chromosomal abnormalities, five de novo, four inherited, and four of unknown inheritance, using Single Nucleotide Polymorphism (SNP) arrays. In all the cases, the patient had an abnormal phenotype. In one familial case and one unknown inheritance case, one of the parents had a phenotype which appeared identical to the patient's phenotype. Additional copy number variants (CNVs) were identified in eight patients. Three patients contained CNVs adjacent to one or either breakpoints. One of these patients showed four and two deletions near the breakpoints of a de novo pericentric inversion. In five patients we identified CNVs on chromosomes unrelated to the previously observed genomic imbalance. These data demonstrate that high-resolution array screening and conventional karyotyping is necessary to tie complex karyotypes to phenotypes of MR patients. (C) 2010 Elsevier Masson SAS. All rights reserved.Show less
SNP array Mental retardation Balanced rearrangements CNV comparative genomic hybridization array-cgh de-novo chromosomal rearrangements clinical-significance dysmorphic features copy number retardation deletions abnormalities
All authors
Gijsbers, A.C.J.; Bosch, C.A.J.; Dauwerse, J.G.; Giromus, O.; Hansson, K.; Hilhorst-Hofstee, Y.; Kriek, M.; Haeringen, A. van; Bijlsma, E.K.; Bakker, E.; Breuning, M.H.; Ruivenkamp, C.A.L.
Date
2010-10-31
Journal
European Journal of Medical Genetics
Volume
53
Issue
5
Pages
227 - 233
DOI
doi:10.1016/j.ejmg.2010.06.003