Reference : Rapid and reliable detection of exon rearrangements in various movement disorders gen...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Rapid and reliable detection of exon rearrangements in various movement disorders genes by multiplex ligation-dependent probe amplification.
Djarmati, Ana* [> >]
Guzvic, Miodrag* [> >]
Grünewald, Anne [> >]
Lang, Anthony E. [> >]
Pramstaller, Peter P. [> >]
Simon, David K. [> >]
Kaindl, Angela M. [> >]
Vieregge, Peter [> >]
Nygren, Anders O. H. [> >]
Beetz, Christian [> >]
Hedrich, Katja [> >]
Klein, Christine [> >]
* These authors have contributed equally to this work.
Movement Disorders
Yes (verified by ORBilu)
United States
[en] Exons ; Gene Rearrangement/genetics ; Humans ; Movement Disorders/classification/genetics ; Nucleic Acid Amplification Techniques/methods ; Polymerase Chain Reaction/methods ; Reproducibility of Results
[en] Because of the occurrence of different types of mutations, comprehensive genetic testing for Parkinson's disease (PD), dopa-responsive dystonia (DRD), and myoclonus-dystonia (M-D) should include screening for small sequence changes and for large exonic rearrangements in disease-associated genes. In diagnostic and research settings, the latter is frequently omitted or performed by laborious and expensive quantitative real-time PCR (qPCR). Our study aimed to evaluate the utility of a novel method, multiplex ligation-dependent probe amplification (MLPA), in molecular diagnostics of movement disorders. We have analyzed, by MLPA, genomic DNA from 21 patients affected with PD, DRD, or M-D, in which the presence of exon rearrangement(s) (n = 20) or of a specific point mutation (detectable by MLPA, n = 1) had been established previously by qPCR or sequencing. In parallel, we have studied, in a blinded fashion, DNA from 49 patients with an unknown mutational status. Exon rearrangements were evident in 20 samples with previously established mutations; in the 21st sample the known specific point mutation was detected. We conclude that MLPA represents a reliable method for large-scale and cost-effective gene dosage screening of various movement disorders genes. This finding reaches far beyond a simple technical advancement and has two major implications: (1) By improving the availability of comprehensive genetic testing, it supports clinicians in the establishment of a genetically defined diagnosis; (2) By enabling gene dosage testing of several genes simultaneously, it significantly facilitates the mutational analysis of large patient and control populations and thereby constitutes the prerequisite for meaningful phenotype-genotype correlations.
Researchers ; Students
(c) 2007 Movement Disorder Society.

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