title: A novel mutation in the spastin gene in a family with spastic paraplegia.
abstract: Hereditary spastic paraplegia (HSP) is a degenerative neuromuscular disease characterized by progressive lower extremity weakness, spasticity and hyperreflexia. Inheritance of HSP is commonly autosomal dominant, spastin was identified as the defective gene in chromosome 2p-linked autosomal dominant hereditary spastic paraplegia (AD-HSP). In a large American family with AD-HSP, we have identified a novel spastin mutation at a splice-acceptor site in intron 6 (1130-1 g--> a) and detected a corresponding aberrant transcript generated from a cryptic splice site. This is predicted to cause a frameshift and premature truncation of the abnormal spastin protein. Our data are the first to confirm that a mutation in an acceptor site in the spastin gene results in activation of a cryptic acceptor site and a translational frameshift. The clinical phenotype of this pedigree is also discussed.
authors.affiliation: Cecil B. Day Laboratory for Neuromuscular Research, Massachusetts General Hospital East, Room 3125, Building 114, 16th Street, Charlestown, MA 02129, USA. morita-jci@umin.ac.jp
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Morita
authors.forename: Mac
authors.initials: M
authors.lastname: Ho
authors.forename: Betsy A
authors.initials: BA
authors.lastname: Hosler
authors.forename: Diane
authors.initials: D
authors.lastname: McKenna-Yasek
authors.forename: Robert H
authors.initials: RH
authors.lastname: Brown
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D010264:Paraplegia / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites; D000074181:Spastin
chemical_list: D002135:Calcium-Binding Proteins; D022821:RNA Splice Sites; D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human