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High resolution profiling of X chromosomal aberrations by array comparative genomic hybridisation
  1. J A Veltman1,*,
  2. H G Yntema1,*,
  3. D Lugtenberg1,
  4. H Arts1,
  5. S Briault2,
  6. E H L P G Huys1,
  7. K Osoegawa3,
  8. P de Jong3,
  9. H G Brunner1,
  10. A Geurts van Kessel1,
  11. H van Bokhoven1,
  12. E F P M Schoenmakers1
  1. 1Department of Human Genetics, University Medical Centre Nijmegen, Nijmegen, The Netherlands
  2. 2Service de Génétique et INSERM U316, Hôpital Bretonneau, Tours, France
  3. 3BACPAC resources, Oakland, CA, USA
  1. Correspondence to:
 J A Veltman PhD
 Department of Human Genetics (417), University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands; j.veltmanantrg.umcn.nl

https://doi.org/10.1136/jmg.2004.018531

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    The causes of mental handicap are highly variable and involve both genetic and environmental factors. Approximately half of the cases have a familial origin, and in 50% of these the genetic defect can be linked to the X chromosome.1 This group of X linked mental retardation patients comprises patients in whom the mental handicap is associated with other clinical features (syndromic or specific mental retardation), and patients in whom the mental deficit is the only consistent clinical or morphogenetic manifestation (non-specific mental retardation, MRX). So far, the molecular basis of MRX is poorly understood because of the extreme genetic heterogeneity of this disorder. Fourteen MRX genes have been identified over the last few years, but each of these account for only a minor fraction of all cases. Since the causative mutation has been identified in only approximately 17% of families,2 it can be estimated that up to 100 MRX genes exist. Most of the currently known MRX genes were identified through the study of microscopically visible X chromosomal abnormalities: OPHN1, TM4SF2, ARHGEF6, and ZNF41 by positional cloning of chromosomal translocation breakpoints,3–6 and FMR2, IL1RAPL1, and FACL4 by chromosome deletion mapping.7–9 In addition, disease related genomic deletions have been identified in other MRX genes and in genes associated with numerous other X linked conditions.

    In our laboratory, four X chromosomal genes associated with a human disorder have been identified based on deletion mapping: REP-1 in choroideremia,10NDP in Norrie disease,11POU3F4 in deafness type 3,12 and RPS6KA6 in mental retardation.13 Deletion mapping, however, is a time consuming method, and standard cytogenetic techniques have a limited resolution of approximately 5–10 Mb. It is a common belief that a number of deletions remain below the detection limit of …

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    Footnotes

    • ↵* The first two authors should be regarded as joint first authors.

    • This work was supported by research grants from the European Communion (QLG3-CT-2002-01810 (EURO-MRX)), and the Brain Foundation of the Netherlands H02.10 (to H G Yntema).

    • Conflict of interest: none declared.