MLPA as first screening method for the detection of microduplications and microdeletions in patients with X-linked mental retardation

Purpose: Routine protocols for the study of mental retardation include karyotype, analysis for fragile X syndrome, and subtelomeric rearrangements. Nevertheless, detection of cryptic rearrangements requires more sensitive techniques. Mutation screening in all known genes responsible for X-linked mental retardation is not feasible, and linkage analysis is sometimes limited. Multiplex ligation probe amplification is a recently developed technique based on the amplification of specific probes that allows relative quantification of 40 to 46 different target DNA sequences in a single reaction. Methods: In the present study, we assessed multiplex ligation probe amplification for the detection of microduplications/microdeletions in 80 male patients with suspicion of X-linked mental retardation. Results: We detected four copy number aberrations (5%): three duplications (GDI1, RPS6KA3, and ARHGEF6) and one deletion (OPHN1). All these changes were confirmed by other molecular techniques, and patients were clinically re-evaluated. Conclusions: We strongly recommend the use of multiplex ligation probe amplification as a first screening method for the detection of copy number aberrations in patients with mental retardation because of its cost-effectiveness.