Chromosomal copy number changes in patients with non-syndromic X linked mental retardation detected by array CGH

• Published in: Journal of medical genetics Vol. 43; no. 4; pp. 362 - 370
• Main Authors: Lugtenberg, D, de Brouwer, A P M, Kleefstra, T, Oudakker, A R, Frints, S G M, Schrander-Stumpel, C T R M, Fryns, J P, Jensen, L R, Chelly, J, Moraine, C, Turner, G, Veltman, J A, Hamel, B C J, de Vries, B B A, van Bokhoven, H, Yntema, H G
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01-04-2006; BMJ; BMJ Publishing Group LTD; BMJ Publishing Group; BMJ Group
• Subjects: Adult and adolescent clinical studies; Array CGH; Artificial chromosomes; BAC; bacterial artificial chromosome; Biochemistry, Molecular Biology; Biological and medical sciences; Cardiology. Vascular system; CGH; Chromosome Aberrations; Cloning; CNP; comparative genomic hybridisation; copy number polymorphism; copy number polymorphisms (CNPs); duplications; Female; FISH; fluorescent in situ hybridisation; FSIQ; full scale intelligence quotient; General aspects. Genetic counseling; Genes; Genome, Human; Genomes; Haplotypes; Humans; Intellectual deficiency; Intellectual disabilities; Life Sciences; Male; Medical genetics; Medical sciences; mental retardation; Mental Retardation, X-Linked - diagnosis; Mental Retardation, X-Linked - genetics; MLPA; MRX; MRXS; multiplex ligated probe amplification; Mutation; non-syndromic X linked mental retardation; Oligonucleotide Array Sequence Analysis - methods; Original; Patients; Polymorphism, Genetic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Sensitivity and Specificity; sequence tagged site; STS; syndromic X linked mental retardation; T/R; test over reference; X chromosomes; X linked mental retardation; XLMR; Human; Sex linked character; Copy number; Intellectual deficiency; Genetics; Patient; Developmental disorder; X-Chromosome; Mental retardation; Genetic disease
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2005.036178

Several studies have shown that array based comparative genomic hybridisation (CGH) is a powerful tool for the detection of copy number changes in the genome of individuals with a congenital disorder. In this study, 40 patients with non-specific X linked mental retardation were analysed with full coverage, X chromosomal, bacterial artificial chromosome arrays. Copy number changes were validated by multiplex ligation dependent probe amplification as a fast method to detect duplications and deletions in patient and control DNA. This approach has the capacity to detect copy number changes as small as 100 kb. We identified three causative duplications: one family with a 7 Mb duplication in Xp22.2 and two families with a 500 kb duplication in Xq28 encompassing the MECP2 gene. In addition, we detected four regions with copy number changes that were frequently identified in our group of patients and therefore most likely represent genomic polymorphisms. These results confirm the power of array CGH as a diagnostic tool, but also emphasise the necessity to perform proper validation experiments by an independent technique.