Communicated by Arnold Munnich
Detection of genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: important role for increased gene dosage of XLMR genes†
Article first published online: 1 JUN 2007
© 2007 Wiley-Liss, Inc.
Volume 28, Issue 10, pages 1034–1042, October 2007
How to Cite
Froyen, G., Van Esch, H., Bauters, M., Hollanders, K., Frints, S. G.M., Vermeesch, J. R., Devriendt, K., Fryns, J.-P. and Marynen, P. (2007), Detection of genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: important role for increased gene dosage of XLMR genes. Hum. Mutat., 28: 1034–1042. doi: 10.1002/humu.20564
- Issue published online: 6 SEP 2007
- Article first published online: 1 JUN 2007
- Manuscript Accepted: 26 APR 2007
- Manuscript Received: 26 FEB 2007
- Instituut voor Innovatie door Wetenschap enTechnologie (IWT), Flanders, Belgium; Fund for Scientific Research–Flanders (FWO-Vlaanderen), Belgium. Grant Number: cG-0229-01
- European Union (EuroMRX Consortium). Grant Number: QLG3-CT-2002-01810.
- mental retardation;
A tiling X-chromosome-specific genomic array with a theoretical resolution of 80 kb was developed to screen patients with idiopathic mental retardation (MR) for submicroscopic copy number differences. Four patients with aberrations previously detected at lower resolution were first analyzed. This facilitated delineation of the location and extent of the aberration at high resolution and subsequently, more precise genotype–phenotype analyses. A cohort of 108 patients was screened, 57 of which were suspected of X-linked mental retardation (XLMR), 26 were probands of brother pairs, and 25 were sporadic cases. A total of 15 copy number changes in 14 patients (13%) were detected, which included two deletions and 13 duplications ranging from 0.1 to 2.7 Mb. The aberrations are associated with the phenotype in five patients (4.6%), based on the following criteria: de novo aberration; involvement of a known or candidate X-linked nonsyndromic(syndromic) MR (MRX(S)) gene; segregation with the disease in the family; absence in control individuals; and skewed X-inactivation in carrier females. These include deletions that contain the MRX(S) genes CDKL5, OPHN1, and CASK, and duplications harboring CDKL5, NXF5, MECP2, and GDI1. In addition, seven imbalances were apparent novel polymorphic regions because they do not fulfill the proposed criteria. Taken together, our data strongly suggest that not only deletions but also duplications on the X chromosome contribute to the phenotype more often than expected, supporting the increased gene dosage mechanism for deregulation of normal cognitive development. Hum Mutat 28(10), 1034–1042, 2007. © 2007 Wiley-Liss, Inc.