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

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• 作者：Christian Beetz ; Rebecca Schü ; le ; Stephan Klebe ; Sven Klimpe ; Thomas Klopstock ; Arnaud Lacour ; Susanne Otto ; Anne-Dorte Sperfeld ; Bart van de Warrenburg ; Ludger Sch&#xf6 ; ls ; Thomas Deufel
• 关键词：CpG methylation ; Hereditary spastic paraplegia ; Mutational hotspot ; NIPA1 ; SPG6
• 刊名：Journal of the Neurological Sciences
• 出版年：2008
• 期刊代码：178_0022510x
• 类别：med
• 出版时间：15 May 2008
• 卷：268
• 期：1-2
• 页码：131-135
• 文件大小：331 K

摘要

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.