X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation
1 Biochemistry and Molecular Genetics Department, Hospital Clínic and IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
2 Genes and Disease Program. Center for Genomic Regulation (CRG-UPF), Barcelona, Spain
3 Microarray Laboratory, Bioinformatics and Genomics Program, (CRG-UPF), Barcelona, Spain
4 Genetics Unit, Universitat Pompeu Fabra, Program in Molecular Medicine and Genetics, Hospital Vall d'Hebron, Barcelona, Spain
5 Unidad de Genética. Hospital Universitario La Fe. Valencia, Spain
6 Laboratori Genètica, UDIAT-Centre Diagnòstic, Corporació Sanitaria Parc Taulí, Institut Universitari Parc Taulí-UAB, Sabadell, Spain
7 Instituto de Biología y Genética Molecular (IBGM-CSIC). Universidad de Valladolid, Spain
8 Unitat de Metabolopaties, Hospital Universitari Materno-Infantil Vall d'Hebron, Spain
9 Molecular Genetics Laboratory, Cruces Hospital, Barakaldo-Bizkaia, Spain
10 GIRMOGEN (Spanish Network for Mental Retardation), Spain
11 Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain
BMC Genomics 2007, 8:443 doi:10.1186/1471-2164-8-443Published: 29 November 2007
Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects.
Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%).
This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients.