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Subtelomere specific microarray based comparative genomic hybridisation: a rapid detection system for cryptic rearrangements in idiopathic mental retardation
  1. N Harada1,2,3,
  2. E Hatchwell4,
  3. N Okamoto5,
  4. M Tsukahara6,
  5. K Kurosawa7,
  6. H Kawame8,
  7. T Kondoh9,
  8. H Ohashi10,
  9. R Tsukino11,
  10. Y Kondoh3,
  11. O Shimokawa3,
  12. T Ida3,
  13. T Nagai12,
  14. Y Fukushima13,
  15. K Yoshiura1,2,
  16. N Niikawa1,2,
  17. N Matsumoto1,2,14
  1. 1Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  2. 2CREST, Japan Science and Technology Corporation, Kawaguchi, Japan
  3. 3Kyushu Medical Science Nagasaki Laboratory, Nagasaki, Japan
  4. 4Genome Research Center, Cold Spring Harbor Laboratory, New York, USA
  5. 5Department of Planning and Research, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan
  6. 6Faculty of Health Science, Yamaguchi University School of Medicine, Ube, Japan
  7. 7Division of Medical Genetics, Kanagawa Children’s Medical Center, Yokohama, Japan
  8. 8Division of Medical Genetics, Nagano Children’s Hospital, Nagano, Japan
  9. 9Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  10. 10Division of Medical Genetics, Saitama Children’s Medical Center, Saitama, Japan
  11. 11Division of Pediatrics, Arida Municipal Hospital, Wakayama, Japan
  12. 12Department of Pediatrics, Koshigaya Hospital, Dokkyo University School of Medicine, Koshigaya, Japan
  13. 13Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan
  14. 14Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  1. Correspondence to:
 Dr N Matsumoto
 Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki 852-8523, Japan;

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Mental retardation (MR) occurs in 2–3% of the general population, and more than half of MR patients are categorised as idiopathic—that is, the cause is unknown.1,2 Patients with idiopathic MR are presumed to be affected with certain genetic disorders or undetectable chromosomal abnormalities. MR may also be caused by environmental factors independently or by their interaction with genetic factors. Subtelomeric rearrangements comprise about half of segmental aneusomies,3 and are one of the major causes of MR.4,5 A recent review showed that subtelomeric rearrangements were detected in 131 (5.1%) of 2585 children with MR.1,4–6 Conventional cytogenetic analysis can detect many, but not all, rearrangements, depending on its powers of resolution.4 Other methods, such as fluorescent in situ hybridisation (FISH) using a complete set of subtelomeric probes, multicolour FISH (M-FISH), comparative genomic hybridisation (CGH), spectrum karyotyping, multiple amplifiable probe hybridisation, primed in situ labelling, and genotyping have been designed to detect subtelomeric rearrangements, but none of them is ideal in terms of sensitivity and/or efficiency.4,6 Microarray based CGH is a promising, high throughput method of detecting subtelomeric rearrangements.4 Veltman et al recently reported a microarray CGH system using crude bacterial/plasmid derived artificial chromosome (BAC/PAC) DNA for the analysis of subtelomeric aberrations, and suggested that degenerate oligonucleotide primed (DOP)-PCR products could also be used instead of crude clone DNA, although the performance of DOP-PCR products might be less sensitive.7 We have developed a microarray CGH system to identify rearrangements involving a subtelomeric region, using DOP-PCR that amplifies subtelomeric BAC/PAC DNA. Here we describe details of the method and the results of microarray CGH analyses of five cases of Wolf-Hirschhorn syndrome (WHS) associated with terminal 4p deletions as positive controls, and of 69 patients with idiopathic MR with or without multiple …

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