Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/20491894http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20491894http://www.w3.org/2000/01/rdf-schema#comment"

Background

mutations in the SPG4/SPAST gene are the most common cause for hereditary spastic paraplegia (HSP). The splice-site mutations make a significant contribution to HSP and account for 17.4% of all types of mutations and 30.8% of point mutations in the SPAST gene. However, only few studies with limited molecular approach were conducted to investigate and decipher the role of SPAST splice-site mutations in HSP.

Methods

a reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and quantitative allele-specific expression assay were performed.

Results

we have characterized the consequence of two novel splice-site mutations (c.1493 + 1G>A and c.1414-1G>A) in the SPAST gene in two different families with pure HSP. The RT-PCR analysis revealed that both spastin mutations are indeed splice-site mutations and cause skipping of exon 12. Furthermore, RT-PCR data suggested that these splice-site mutations may cause leaky splicing. By means of a quantitative allele-specific expression assay, we could confirm that both splice-site mutations cause leaky splicing, as the relative expression of the exon 12-skipped transcript was reduced (21.1 ± 3.6 compared to expected 50%).

Conclusions

our finding supports a "threshold-effect-model" for functional spastin in HSP. A higher level (78.8 ± 3.9%) of functional spastin than the expected ratio of 50% owing to leaky splicing might cause late age at onset of HSP. Remarkably, we could show that a quantitative allele-specific expression assay is a simple and effective tool to evaluate the role of most types of spastin splice-site mutations in HSP."xsd:string
http://purl.uniprot.org/citations/20491894http://purl.org/dc/terms/identifier"doi:10.1111/j.1468-1331.2010.03079.x"xsd:string
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/author"Zibat A."xsd:string
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/author"Shoukier M."xsd:string
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/author"Sauter S.M."xsd:string
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/author"Zechner U."xsd:string
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/author"Klimpe S."xsd:string
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/author"Wellek B."xsd:string
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/author"Mannan A.U."xsd:string
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/author"Pantakani D.V."xsd:string
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/name"Eur J Neurol"xsd:string
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/pages"99-105"xsd:string
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/title"Evaluating the effect of spastin splice mutations by quantitative allele-specific expression assay."xsd:string
http://purl.uniprot.org/citations/20491894http://purl.uniprot.org/core/volume"18"xsd:string
http://purl.uniprot.org/citations/20491894http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20491894
http://purl.uniprot.org/citations/20491894http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20491894
http://purl.uniprot.org/uniprot/#_B4E267-mappedCitation-20491894http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20491894
http://purl.uniprot.org/uniprot/#_E5KRP5-mappedCitation-20491894http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20491894
http://purl.uniprot.org/uniprot/#_E5KRP6-mappedCitation-20491894http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20491894
http://purl.uniprot.org/uniprot/#_Q9UBP0-mappedCitation-20491894http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20491894
http://purl.uniprot.org/uniprot/E5KRP6http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/20491894
http://purl.uniprot.org/uniprot/E5KRP5http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/20491894
http://purl.uniprot.org/uniprot/Q9UBP0http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/20491894
▶