Source:http://linkedlifedata.com/resource/pubmed/id/18190593
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
2008-2-13
|
| pubmed:abstractText |
The SPG4 gene is frequently mutated in autosomal dominant form of hereditary spastic paraplegia (HSP). We report that the compound heterozygous sequence variants S44L, a known polymorphism, and c.1687G>A, a novel mutation in SPG4 cause a severe form of HSP in a patient. The family members carrying solely c.1687G>A mutation are asymptomatic for HSP. The reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that the c.1687G>A mutation is a splice site mutation and causes skipping of the exon 15 of spastin. Furthermore, quantification of RT-PCR products by sequencing and quantification of allele-specific expression by pyrosequencing assay revealed that c.1687G>A is a leaky or hypomorphic splice site mutation. At the protein level, c.1687G>A mutation in SPG4 leads to E563K substitution. In ex vivo study, about 10% of cells expressing E563K mutant spastin showed filamentous expression pattern, suggesting a hypomorphic effect at the protein level. Collectively, our results suggest that S44L in association with c.1687G>A (E563K) drops the functional level of spastin below a threshold limit sufficient to manifest HSP.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
1399-0004
|
| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
73
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
268-72
|
| pubmed:meshHeading |
pubmed-meshheading:18190593-Adenosine Triphosphatases,
pubmed-meshheading:18190593-Alleles,
pubmed-meshheading:18190593-Amino Acid Substitution,
pubmed-meshheading:18190593-Base Sequence,
pubmed-meshheading:18190593-Computational Biology,
pubmed-meshheading:18190593-DNA Mutational Analysis,
pubmed-meshheading:18190593-European Continental Ancestry Group,
pubmed-meshheading:18190593-Exons,
pubmed-meshheading:18190593-Female,
pubmed-meshheading:18190593-Gene Expression Regulation,
pubmed-meshheading:18190593-Germany,
pubmed-meshheading:18190593-HeLa Cells,
pubmed-meshheading:18190593-Heterozygote,
pubmed-meshheading:18190593-Humans,
pubmed-meshheading:18190593-Intracellular Space,
pubmed-meshheading:18190593-Male,
pubmed-meshheading:18190593-Molecular Sequence Data,
pubmed-meshheading:18190593-Mutation,
pubmed-meshheading:18190593-Pedigree,
pubmed-meshheading:18190593-Polymorphism, Single Nucleotide,
pubmed-meshheading:18190593-Protein Transport,
pubmed-meshheading:18190593-RNA, Messenger,
pubmed-meshheading:18190593-RNA Splice Sites,
pubmed-meshheading:18190593-Spastic Paraplegia, Hereditary
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
Compound heterozygosity in the SPG4 gene causes hereditary spastic paraplegia.
|
| pubmed:affiliation |
Institute of Human Genetics, University of Goettingen, Goettingen, Germany.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|