6533b862fe1ef96bd12c778d
RESEARCH PRODUCT
Screening of hereditary spastic paraplegia patients for alterations at NIPA1 mutational hotspots.
Bart P.c. Van De WarrenburgArnaud LacourThomas KlopstockLudger SchölsAnne-dorte SperfeldThomas DeufelSven KlimpeS. OttoStephan KlebeChristian BeetzRebecca Schülesubject
Hereditary spastic paraplegiaDNA Mutational AnalysisMolecular Sequence DataCohort StudiesDegenerative diseaseCognitive neurosciences [UMCN 3.2]Polymorphism (computer science)DNA Mutational AnalysismedicineHumansGenetic TestingGeneGeneticsbusiness.industrySpastic Paraplegia HereditaryMembrane ProteinsMethylationDNA Methylationmedicine.diseaseNeurologyDNA methylationNeurology (clinical)Restriction fragment length polymorphismbusinessFunctional Neurogenomics [DCN 2]Polymorphism Restriction Fragment Lengthdescription
Item does not contain fulltext 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2008-01-01 | Journal of the Neurological Sciences |