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Review
. 2012;13(3):3245-3276.
doi: 10.3390/ijms13033245. Epub 2012 Mar 8.

Use of the MLPA assay in the molecular diagnosis of gene copy number alterations in human genetic diseases

Liborio Stuppia  1 , Ivana Antonucci  1 , Giandomenico Palka  1 , Valentina Gatta  1
Affiliations
Review

Use of the MLPA assay in the molecular diagnosis of gene copy number alterations in human genetic diseases

Liborio Stuppia et al. Int J Mol Sci. 2012.

Abstract

Multiplex Ligation-dependent Probe Amplification (MLPA) assay is a recently developed technique able to evidence variations in the copy number of several human genes. Due to this ability, MLPA can be used in the molecular diagnosis of several genetic diseases whose pathogenesis is related to the presence of deletions or duplications of specific genes. Moreover, MLPA assay can also be used in the molecular diagnosis of genetic diseases characterized by the presence of abnormal DNA methylation. Due to the large number of genes that can be analyzed by a single technique, MLPA assay represents the gold standard for molecular analysis of all pathologies derived from the presence of gene copy number variation. In this review, the main applications of the MLPA technique for the molecular diagnosis of human diseases are described.

Keywords: CNV; MLPA; gene copy number; genetic disease; molecular diagnosis.

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Figures

Figure 1
Figure 1
Multiplex Ligation-dependent Probe Amplification (MLPA) analysis of the Duchenne Muscular Dystrophy (DMD) gene. Abscissa represents DMD gene and control probes (c); ordinate represents fluorescent intensity of amplification. For each probe, the ratio <0.75 stands for deletion; and the ratio >1.3 stands for duplication. (a) MLPA analysis showing a heterozygous deletion of exons 46–50 (ratio < 0.75) of the DMD gene in the mother of an affected patient; (b) Normal control (075 < ratio < 1.3).
Figure 2
Figure 2
MLPA analysis of the PMP22 gene. Abscissa represents PMP22 gene and control probes (c); ordinate represents fluorescent intensity of amplification. For each probe, the ratio <0.75 stands for deletion; and the ratio >1.3 stands for duplication. (a) duplication of the PMP22 gene (ratio > 1.3) in a patients affected by Charcot Marie Thoot (CMT) disease; (b) Normal control (075 < ratio < 1.3).
Figure 2
Figure 2
MLPA analysis of the PMP22 gene. Abscissa represents PMP22 gene and control probes (c); ordinate represents fluorescent intensity of amplification. For each probe, the ratio <0.75 stands for deletion; and the ratio >1.3 stands for duplication. (a) duplication of the PMP22 gene (ratio > 1.3) in a patients affected by Charcot Marie Thoot (CMT) disease; (b) Normal control (075 < ratio < 1.3).
See this image and copyright information in PMC

References

    1. Armour J.A., Barton D.E., Cockburn D.J., Taylor G.R. The detection of large deletions or duplications in genomic DNA. Hum. Mutat. 2002;20:325–337. - PubMed
    1. den Dunnen J.T., Grootscholten P.M., Bakker E., Blonden L.A., Ginjaar H.B., Wapenaar M.C., van Paassen H.M., van Broeckhoven C., Pearson P.L., van Ommen G.J. Topography of the Duchenne muscular dystrophy (DMD) gene: FIGE and cDNA analysis of 194 cases reveals 115 deletions and 13 duplications. Am. J. Hum. Genet. 1989;45:835–847. - PMC - PubMed
    1. van der Steege G., Grootscholten P.M., van der Vlies P., Draaijers T.G., Osinga J., Cobben J.M., Scheffer H., Buys C.H. PCR based DNA test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy. Lancet. 1995;345:985–986. - PubMed
    1. Lee C., Iafrate A.J., Brothman A.R. Copy number variations and clinical cytogenetic diagnosis of constitutional disorders. Nat. Genet. 2007;39:548–554. - PubMed
    1. Choy K.W., Setlur S.R., Lee C., Lau T.K. The impact of human copy number variation on a new era of genetic testing. BJOG. 2010;117:391–398. - PubMed