Array-Based MLPA to Detect Recurrent Copy Number Variations in Patients With Idiopathic Mental Retardation

作者：Rooms Lie**eth; Vandeweyer Geert; Reyniers Edwin; van Mol Kurt; de Canck Ilse; Van der Aa Nathalie; Rossau Rudi; Kooy R Frank^*

来源：American Journal of Medical Genetics, Part A, 2011, 155A(2): 343-348.

DOI：10.1002/ajmg.a.33810

• copy number variation
• mental retardation
• array-based MLPA

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.

• 出版日期2011-2