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PMID: 16169931 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Validation Study

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

Journal of medical genetics ·Vol. 43 ·No. 4 ·2006-04-00 ·Pages 362-70

Lugtenberg D, de Brouwer AP, Kleefstra T, Oudakker AR, Frints SG, Schrander-Stumpel CT, Fryns JP, Jensen LR, Chelly J, Moraine C, Turner G, Veltman JA, Hamel BC, de Vries BB, van Bokhoven H, Yntema HG

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.

MeSH Terms
Chromosome Aberrations Female Genome, Human Haplotypes Humans Male Mental Retardation, X-Linked/diagnosis,genetics Oligonucleotide Array Sequence Analysis/methods Polymorphism, Genetic Sensitivity and Specificity
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Lugtenberg D
Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
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
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Article Info
Journal
Journal of medical genetics
Abbr.
J Med Genet
ISSN
1468-6244
DOI
10.1136/jmg.2005.036178
Published
2006-04-00
Epub
2005-00-16
Pages
362-70
Language
English
Region
England
NLM ID
2985087R
PMCID
PMC2563232
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1136/jmg.2005.036178 PMC Full Text View journal details
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