PT - JOURNAL ARTICLE AU - R H Scott AU - J Douglas AU - L Baskcomb AU - A O Nygren AU - J M Birch AU - T R Cole AU - V Cormier-Daire AU - D M Eastwood AU - S Garcia-Minaur AU - P Lupunzina AU - K Tatton-Brown AU - J Bliek AU - E R Maher AU - N Rahman TI - Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) robustly detects and distinguishes 11p15 abnormalities associated with overgrowth and growth retardation AID - 10.1136/jmg.2007.053207 DP - 2008 Feb 01 TA - Journal of Medical Genetics PG - 106--113 VI - 45 IP - 2 4099 - http://jmg.bmj.com/content/45/2/106.short 4100 - http://jmg.bmj.com/content/45/2/106.full SO - J Med Genet2008 Feb 01; 45 AB - 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.