Screening of hereditary spastic paraplegia patients for alterations at NIPA1 mutational hotspots

Abstract Mutations in NIPA1 cause hereditary spastic paraplegia type 6 ( SPG6 HSP). Sequencing of the whole gene has revealed alterations of either of two nucleotides in eight of nine SPG6 HSP families reported to date. By analysing CpG methylation, we provide a mechanistic explanation for a mutatio...

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Bibliographic Details
Published in:Journal of the neurological sciences 2008-05, Vol.268 (1), p.131-135
Main Authors: Beetz, Christian, Schüle, Rebecca, Klebe, Stephan, Klimpe, Sven, Klopstock, Thomas, Lacour, Arnaud, Otto, Susanne, Sperfeld, Anne-Dorte, van de Warrenburg, Bart, Schöls, Ludger, Deufel, Thomas
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cohort Studies
CpG methylation
DNA Methylation
DNA Mutational Analysis
Genetic Testing - methods
Hereditary spastic paraplegia
Humans
Medical sciences
Membrane Proteins - genetics
Molecular Sequence Data
Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis
Mutational hotspot
Neurology
NIPA1
Polymorphism, Restriction Fragment Length - genetics
Spastic Paraplegia, Hereditary - genetics
SPG6
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Summary:Abstract Mutations in NIPA1 cause hereditary spastic paraplegia type 6 ( SPG6 HSP). Sequencing of the whole gene has revealed alterations of either of two nucleotides in eight of nine SPG6 HSP families reported to date. By analysing CpG methylation, we provide a mechanistic explanation for a mutational hotspot to underlie frequent alteration of one of these nucleotides. We also developed PCR RFLP assays to detect recurrent NIPA1 changes and screened 101 independent HSP patients, including 45 index patients of autosomal dominant HSP families. Our negative finding in this cohort for which several other causes of HSP had been excluded suggests NIPA1 alterations at mutational hotspots to be less frequent than previously thought. Nevertheless, the assays introduced represent a valid pre-screen easily implementable in the molecular diagnosis of HSP.
ISSN:0022-510X
1878-5883
DOI:10.1016/j.jns.2007.11.015