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The performance of CGH array for the detection of cryptic constitutional chromosome imbalances
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  1. J Schoumans1,
  2. B-M Anderlid1,
  3. E Blennow1,
  4. B T Teh2,
  5. M Nordenskjöld1
  1. 1Department of Molecular Medicine, Clinical Genetics Unit, Karolinska Institute, CMM L8:02 Karolinska Hospital, SE-17176 Stockholm, Sweden
  2. 2Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA
  1. Correspondence to:
 Jacqueline Schoumans;
 Jacqueline.schoumanscmm.ki.se

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Gene dose alterations can cause mental retardation (MR), congenital malformations and miscarriages. Standard chromosome analysis by G-banding has a limited resolution, but molecular cytogenetic techniques, such as multi-subtelomeric FISH, microdeletion FISH, multicolour FISH and comparative genomic hybridisation (CGH), have played an important role for the diagnosis of MR during the past decade.1 A complete set of subtelomeric FISH probes was presented in 1996 and updated in 2000.2 Consequently, screening for subtelomeric abnormalities has become a diagnostic test that is offered by diagnostic laboratories, and a number of studies reporting new subtelomeric rearrangements have been published.3–16 However, these probes only reveal chromosome rearrangements located in the subtelomeric region. To cover the whole genome, genome wide screening for chromosomal imbalances using microsatellite markers has been reported,17,18 as well as metaphase CGH.19–22 Yet none of these techniques is able to offer a high resolution screening of the whole genome for chromosome imbalances. The development of accurate and sensitive genome wide screening methods would facilitate the clinical diagnosis of patients with very small or subtle rearrangements. Screening for chromosomal imbalances by array CGH, whether using cDNA23 or BAC clones,24 has mainly been performed on cancer samples,25–30 which usually contain large gene dose alterations. Although array CGH has provided a higher resolution compared to conventional CGH, it has not yet become a widely applied method for the analysis of gene dose alterations in individuals with idiopathic mental retardation. It has been a challenge to achieve the adequate performance needed for the reliable detection of single copy losses or gains of very small regions. Chromosome specific micro-arrays have however been used in a few cases to determine the critical regions in microdeletion disorders.31,32 In this report we used a cDNA micro-array and …

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