MLPA as first screening method for the detection of microduplications and microdeletions in patients with X-linked mental retardation.
OBJECTIVE
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.
Madrigal
Irene
I
Biochemistry and Molecular Genetics Department, Hospital Clínic, Barcelona, Spain.
Rodríguez-Revenga
Laia
L
Badenas
Celia
C
Sánchez
Aurora
A
Martinez
Francisco
F
Fernandez
Isabel
I
Fernández-Burriel
Miguel
M
Fernández-Buriel
Miguel
M
Milà
M
M
D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X / Q000235:genetics*; D017931:DNA Primers; D015342:DNA Probes / Q000235:genetics; D020440:Gene Duplication; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D010375:Pedigree; D017384:Sequence Deletion / Q000235:genetics*
D017931:DNA Primers; D015342:DNA Probes