title: Chromosomal copy number changes in patients with non-syndromic X linked mental retardation detected by array CGH.
abstract: 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.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Lugtenberg
authors.forename: A P M
authors.initials: AP
authors.lastname: de Brouwer
authors.forename: T
authors.initials: T
authors.lastname: Kleefstra
authors.forename: A R
authors.initials: AR
authors.lastname: Oudakker
authors.forename: S G M
authors.initials: SG
authors.lastname: Frints
authors.forename: C T R M
authors.initials: CT
authors.lastname: Schrander-Stumpel
authors.forename: J P
authors.initials: JP
authors.lastname: Fryns
authors.forename: L R
authors.initials: LR
authors.lastname: Jensen
authors.forename: J
authors.initials: J
authors.lastname: Chelly
authors.forename: C
authors.initials: C
authors.lastname: Moraine
authors.forename: G
authors.initials: G
authors.lastname: Turner
authors.forename: J A
authors.initials: JA
authors.lastname: Veltman
authors.forename: B C J
authors.initials: BC
authors.lastname: Hamel
authors.forename: B B A
authors.initials: BB
authors.lastname: de Vries
authors.forename: H
authors.initials: H
authors.lastname: van Bokhoven
authors.forename: H G
authors.initials: HG
authors.lastname: Yntema
mesh_terms: D002869:Chromosome Aberrations; D005260:Female; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000175:diagnosis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011110:Polymorphism, Genetic; D012680:Sensitivity and Specificity