RT Journal Article
SR Electronic
T1 Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) robustly detects and distinguishes 11p15 abnormalities associated with overgrowth and growth retardation
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 106
OP 113
DO 10.1136/jmg.2007.053207
VO 45
IS 2
A1 Scott, R H
A1 Douglas, J
A1 Baskcomb, L
A1 Nygren, A O
A1 Birch, J M
A1 Cole, T R
A1 Cormier-Daire, V
A1 Eastwood, D M
A1 Garcia-Minaur, S
A1 Lupunzina, P
A1 Tatton-Brown, K
A1 Bliek, J
A1 Maher, E R
A1 Rahman, N
YR 2008
UL http://jmg.bmj.com/content/45/2/106.abstract
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.