| Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia. | |
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MedLine Citation:
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PMID: 11985387 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We studied nine Italian families with a pure form of autosomal dominant spastic paraplegia (ADHSP) to assess the frequency of mutations in the SPG4 gene. We observed marked intrafamilial variability in both age-at-onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55 years to healthy carriers of the mutation after age 70. Four of nine probands harboured SPG4 mutations, We identified three new SPG4 mutations, all predicting a loss-of-func-tion with apparently important consequences for spastin function. RT-PCR studies predict loss-of-function as a possible mechanism leading to spastin-related HSP. The current study expands the spectrum of allelic variants in SPG4, confirming their pathological significance in pure AD-HSP and suggesting implications for the presumed function of spastin. |
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Authors:
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Clarice Patrono; Carlo Casali; Alessandra Tessa; Federica Cricchi; Daniela Fortini; Rosalba Carrozzo; Gabriele Siciliano; Enrico Bertini; Filippo M Santorelli |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of neurology Volume: 249 ISSN: 0340-5354 ISO Abbreviation: J. Neurol. Publication Date: 2002 Feb |
Date Detail:
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Created Date: 2002-05-02 Completed Date: 2002-10-16 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0423161 Medline TA: J Neurol Country: Germany |
Other Details:
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Languages: eng Pagination: 200-5 Citation Subset: IM |
Affiliation:
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IRCCS-Children's Hospital Bambino Gesù, Rome, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphatases
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genetics*,
metabolism Adolescent Adult Age of Onset Aged Alternative Splicing / genetics* Amino Acid Sequence / genetics Child Child, Preschool Chromosomes, Human, Pair 2 DNA Mutational Analysis Exons / genetics Female Gene Frequency / genetics Genetic Testing Humans Infant Italy Male Middle Aged Mutation, Missense / genetics* Pedigree RNA, Messenger / genetics* Spastic Paraplegia, Hereditary / genetics*, physiopathology |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; EC 3.6.1.-/Adenosine Triphosphatases; EC 3.6.1.-/SPAST protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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