Molecular karyotyping of patients with MCA/MR: the blurred boundary between normal and pathogenic variationde Ravel T.J.L. · Balikova I. · Thienpont B. · Hannes F. · Maas N. · Fryns J.-P. · Devriendt K. · Vermeesch J.R.
Centre for Human Genetics, UZ Gasthuisberg, Leuven (Belgium)
Molecular karyotyping has revealed that microdeletions/duplications in the human genome are a major cause of multiple congenital anomalies associated with mental retardation (MCA/MR). The identification of a de novo chromosomal imbalance in a patient with MCA/MR is usually considered causal for the phenotype while a chromosomal imbalance inherited from a phenotypically normal parent is considered as a benign variation and not related to the disorder. Around 40% of imbalances in patients with MCA/MR in this series is inherited from a healthy parent and the majority of these appear to be (extremely) rare variants. As some of these contain known disease-causing genes and have also been found to be de novo in MCA/MR patients, this challenges the general view that such familial variants are innocent and of no major phenotypic consequence. Rather, we argue, that human genomes can be tolerant of genomic copy number variations depending on the genetic and environmental background and that different mechanisms play a role in determining whether these chromosomal imbalances manifest themselves.
Request reprints from Professor Dr. J.R. Vermeesch
Centre for Human Genetics
UZ Gasthuisberg, Herestraat 49
BE–3000 Leuven (Belgium);
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Manuscript received: 23 April 2006
Accepted in original form for publication by A. Geurts van Kessel,: 2 May 2006.
Number of Print Pages : 6
Number of Figures : 0, Number of Tables : 1, Number of References : 26
Cytogenetic and Genome Research
Vol. 115, No. 3-4, Year 2006 (Cover Date: November 2006)
Journal Editor: Schmid, M. (Würzburg)
ISSN: 1424–8581 (print), 1424–859X (Online)
For additional information: http://www.karger.com/CGR