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 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.

• Authors: Christian Beetz, Rebecca Schüle, Stephan Klebe, Sven Klimpe, Thomas Klopstock, Arnaud Lacour, Susanne Otto, Anne-Dorte Sperfeld, Bart van de Warrenburg, Ludger Schöls, Thomas Deufel
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 268 Issue 1-2 Pg. 131-5 (May 15 2008) ISSN: 0022-510X [Print] Netherlands
• PMID: 18191948 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• NIPA1 protein, human

Topics

• Cohort Studies
• DNA Methylation
• DNA Mutational Analysis
• Genetic Testing (methods)
• Humans
• Membrane Proteins (genetics)
• Molecular Sequence Data
• Polymorphism, Restriction Fragment Length (genetics)
• Spastic Paraplegia, Hereditary (genetics)