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Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) robustly detects and distinguishes 11p15 abnormalities associated with overgrowth and growth retardation
  1. R H Scott1,
  2. J Douglas1,
  3. L Baskcomb1,
  4. A O Nygren2,
  5. J M Birch3,
  6. T R Cole4,11,
  7. V Cormier-Daire5,
  8. D M Eastwood6,
  9. S Garcia-Minaur7,
  10. P Lupunzina8,
  11. K Tatton-Brown9,
  12. J Bliek10,
  13. E R Maher11,
  14. N Rahman1
  1. 1
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK
  2. 2
    MRC-Holland, Amsterdam, The Netherlands
  3. 3
    Cancer Research UK Paediatric and Familial Cancer Research Group, Royal Manchester Children’s Hospital, Manchester, UK
  4. 4
    Clinical Genetics Unit, Birmingham Women’s Hospital, Birmingham, UK
  5. 5
    Department of Medical Genetics, Hopital Necker Enfants Malades, Paris, France
  6. 6
    Department of Orthopaedic Surgery, Great Ormond Street Hospital, London, UK
  7. 7
    Kennedy-Galton Centre, North West Thames Regional Genetics Service, UK
  8. 8
    Department of Genetics, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain
  9. 9
    Department of Clinical Genetics, St George’s Hospital NHS Trust, London, UK
  10. 10
    Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands
  11. 11
    Department of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham, Birmingham UK
  1. Dr Richard Scott, Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, UK, SM2 5NG, UK; richard.scott{at}


Background: A variety of abnormalities have been demonstrated at chromosome 11p15 in individuals with overgrowth and growth retardation. The identification of these abnormalities is clinically important but often technically difficult. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is a simple but effective technique able to identify and differentiate methylation and copy number abnormalities, and thus is potentially well suited to the analysis of 11p15.

Aims: To customise and test an MS-MLPA assay capable of detecting and distinguishing the full spectrum of known 11p15 epigenetic and copy number abnormalities associated with overgrowth and growth retardation and to assess its effectiveness as a first line investigation of these abnormalities.

Methods: Five synthetic probe pairs were designed to extend the range of abnormalities detectable with a commercially available MS-MLPA assay. To define the normal values, 75 normal control samples were analysed using the customised assay. The assay was then used to analyse a “test set” of 24 normal and 27 abnormal samples, with data analysed by two independent blinded observers. The status of all abnormal samples was confirmed by a second technique.

Results: The MS-MLPA assay gave reproducible, accurate methylation and copy number results in the 126 samples assayed. The blinded observers correctly identified and classified all 51 samples in the test set.

Conclusions: MS-MLPA robustly and sensitively detects and distinguishes epigenetic and copy number abnormalities at 11p15 and is an effective first line investigation of 11p15 in individuals with overgrowth or growth retardation.

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  • Additional data are published online only at

  • Funding: This work was supported by the Institute of Cancer Research (UK). RHS is supported by a grant which forms part of the Michael and Betty Kadoorie Cancer Genetics Research Programme.

  • Competing interests: None.