title: Array-based MLPA to detect recurrent copy number variations in patients with idiopathic mental retardation.
abstract: Microdeletions, either subtelomeric or interstitial, are responsible for the mental handicap in approximately 10-20% of all patients. Currently, Multiplex Ligation-dependent Probe Amplification (MLPA) is widely used to detect these small aberrations in a routine fashion. Although cost-effective, the throughput is low and the degree of multiplexing is limited to maximally 40-50 probes. Therefore, we developed an array-based MLPA method, with probes identified by unique tag sequences, allowing the simultaneous analysis of 180 probes in a single experiment thereby covering all known mental retardation loci with at least two probes. We screened 120 patients with idiopathic mental retardation. In this group we detected 6 aberrations giving a detection rate of 5%, consistent with similar studies. In addition we tested 293 patients with mental retardation who were negative for fragile X syndrome and commercially available subtelomeric MLPA. We found seven causative rearrangements in this group (detection rate of 2.4%) thereby illustrating the value of including probes for interstitial microdeletion syndromes and additional probes in the telomeric regions in targeted screening sets for mental retardation. Array-based MLPA may thus be a good candidate to develop probe sets that rapidly detect copy number changes of disease associated loci in the human genome. This method may become a valuable tool in a routine diagnostic setting as it is a fast, user-friendly and relatively low-cost technique providing straightforward results requiring only 125 ng of genomic DNA.
authors.affiliation: Department of Medical Genetics, University of Antwerp and University Hospital, Antwerp, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Rooms
authors.forename: Geert
authors.initials: G
authors.lastname: Vandeweyer
authors.forename: Edwin
authors.initials: E
authors.lastname: Reyniers
authors.forename: Kurt
authors.initials: K
authors.lastname: van Mol
authors.forename: Ilse
authors.initials: I
authors.lastname: de Canck
authors.forename: Nathalie
authors.initials: N
authors.lastname: Van der Aa
authors.forename: Rudi
authors.initials: R
authors.lastname: Rossau
authors.forename: R Frank
authors.initials: RF
authors.lastname: Kooy
mesh_terms: D000465:Algorithms; D002872:Chromosome Deletion; D017931:DNA Primers / Q000235:genetics; D015342:DNA Probes / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D046228:Microarray Analysis / Q000379:methods*
chemical_list: D017931:DNA Primers; D015342:DNA Probes