Copyright © 2007 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 81, Issue 4, 768-779, 1 October 2007
doi:10.1086/521274
Article
Copy-Number Variations Measured by Single-Nucleotide–Polymorphism Oligonucleotide Arrays in Patients with Mental Retardation
Janine Wagenstallera, b, Stephanie Sprangerd, Bettina Lorenz-Depiereuxa, b, Bernd Kazmierczakd, Michaela Nathrathc, Dagmar Wahle, Babett Heyeb, Dieter Gläserf, Volkmar Liebscherg, Thomas Meitingera, b and Tim M. Stromb, 
, 
a From the Institute of Human Genetics, GSF National Research Center for Environment and Health, Munich-Neuherberg, Germany
b Institute of Human Genetics, Technical University, Munich
c Department of Pediatrics, Technical University, Munich
d Praxis für Humangenetik, Bremen, Germany
e Praxis für Humangenetische Beratung, Augsburg, Germany
f Zentrum für Humangenetik, Neu-Ulm, Germany
g Department of Mathematics and Computer Science, University Greifswald, Greifswald, Germany
Address for correspondence and reprints: Dr. Tim M. Strom, Institute of Human Genetics, GSF National Research Center, Ingolstädter Landstrasse 1, 85764 Neuherberg, GermanyAbstract
Whole-genome analysis using high-density single-nucleotide–polymorphism oligonucleotide arrays allows identification of microdeletions, microduplications, and uniparental disomies. We studied 67 children with unexplained mental retardation with normal karyotypes, as assessed by G-banded chromosome analyses. Their DNAs were analyzed with Affymetrix 100K arrays. We detected 11 copy-number variations that most likely are causative of mental retardation, because they either arose de novo (9 cases) and/or overlapped with known microdeletions (2 cases). The eight deletions and three duplications varied in size from 200 kb to 7.5 Mb. Of the 11 copy-number variations, 5 were flanked by low-copy repeats. Two of those, on chromosomes 15q25.2 and Xp22.31, have not been described before and have a high probability of being causative of new deletion and duplication syndromes, respectively. In one patient, we found a deletion affecting only a single gene, MBD5, which codes for the methyl-CpG-binding domain protein 5. In addition to the 67 children, we investigated 4 mentally retarded children with apparent balanced translocations and detected four deletions at breakpoint regions ranging in size from 1.1 to 14 Mb.
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