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| Diagnostic genome profiling in mental retardation |
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| Author(s): de Vries BBA, Pfundt R, Leisink M, Koolen DA, Vissers LELM, Janssen IM, van Reijmersdal S, Nillesen WM, Huys EHLPG, de Leeuw N, Smeets D, Sistermans EA, Feuth T, van Ravenswaaij-Arts CMA, van Kessel AG, Schoenmakers EFPM, Brunner HG, Veltman JA |
| Source: AMERICAN JOURNAL OF HUMAN GENETICS Volume: 77 Issue: 4 Pages: 606-616 Published: OCT 2005 |
| Times Cited: 219 References: 36 |
| Abstract: 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 similar to 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: de Vries, BBA (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, POB 9101, NL-6500 HB Nijmegen, Netherlands |
Addresses:
1. Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands
2. Radboud Univ Nijmegen, Med Ctr, Dept Biophys, NL-6500 HB Nijmegen, Netherlands
3. Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands |
| Publisher: UNIV CHICAGO PRESS, 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA |
| Subject Category: Genetics & Heredity |
| IDS Number: 967QS |
| ISSN: 0002-9297 |
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