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Publication year
2005Author(s)
Source
American Journal of Human Genetics, 77, 4, (2005), pp. 606-16ISSN
Publication type
Article / Letter to editor
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Organization
Human Genetics
Dermatology
Cognitive Neuroscience
Health Evidence
Former Organization
Medical Physics and Biophysics
Epidemiology, Biostatistics & HTA
Journal title
American Journal of Human Genetics
Volume
vol. 77
Issue
iss. 4
Page start
p. 606
Page end
p. 16
Subject
Biophysics; DCN 2: Functional Neurogenomics; DCN 3: Neuroinformatics; EBP 2: Effective Hospital Care; IGMD 3: Genomic disorders and inherited multi-system disorders; NCMLS 6: Genetics and epigenetic pathways of disease; ONCOL 1: Hereditary cancer and cancer-related syndromes; ONCOL 3: Translational research; UMCN 1.2: Molecular diagnosis, prognosis and monitoring; UMCN 1.5: Interventional oncologyAbstract
Mental retardation (MR) occurs in 2%-3% of the general population. Conventional karyotyping has a resolution of 5-10 million bases and detects chromosomal alterations in approximately 5% of individuals with unexplained MR. The frequency of smaller submicroscopic chromosomal alterations in these patients is unknown. Novel molecular karyotyping methods, such as array-based comparative genomic hybridization (array CGH), can detect submicroscopic chromosome alterations at a resolution of 100 kb. In this study, 100 patients with unexplained MR were analyzed using array CGH for DNA copy-number changes by use of a novel tiling-resolution genomewide microarray containing 32,447 bacterial artificial clones. Alterations were validated by fluorescence in situ hybridization and/or multiplex ligation-dependent probe amplification, and parents were tested to determine de novo occurrence. Reproducible DNA copy-number changes were present in 97% of patients. The majority of these alterations were inherited from phenotypically normal parents, which reflects normal large-scale copy-number variation. In 10% of the patients, de novo alterations considered to be clinically relevant were found: seven deletions and three duplications. These alterations varied in size from 540 kb to 12 Mb and were scattered throughout the genome. Our results indicate that the diagnostic yield of this approach in the general population of patients with MR is at least twice as high as that of standard GTG-banded karyotyping.
This item appears in the following Collection(s)
- Academic publications [238441]
- Electronic publications [122523]
- Faculty of Medical Sciences [90373]
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