title: Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) robustly detects and distinguishes 11p15 abnormalities associated with overgrowth and growth retardation.
abstract: 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.
  
  
  OBJECTIVE
  To customize 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 customized 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.
authors.forename: R H
authors.initials: RH
authors.lastname: Scott
authors.forename: J
authors.initials: J
authors.lastname: Douglas
authors.forename: L
authors.initials: L
authors.lastname: Baskcomb
authors.forename: A O
authors.initials: AO
authors.lastname: Nygren
authors.forename: J M
authors.initials: JM
authors.lastname: Birch
authors.forename: T R
authors.initials: TR
authors.lastname: Cole
authors.forename: V
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: D M
authors.initials: DM
authors.lastname: Eastwood
authors.forename: S
authors.initials: S
authors.lastname: Garcia-Minaur
authors.forename: P
authors.initials: P
authors.lastname: Lupunzina
authors.forename: K
authors.initials: K
authors.lastname: Tatton-Brown
authors.forename: J
authors.initials: J
authors.lastname: Bliek
authors.forename: E R
authors.initials: ER
authors.lastname: Maher
authors.forename: N
authors.initials: N
authors.lastname: Rahman
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D018628:Gene Dosage; D018392:Genomic Imprinting; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D015336:Molecular Probe Techniques; D021141:Nucleic Acid Amplification Techniques