title: Spastin gene mutations in Bulgarian patients with hereditary spastic paraplegia.
abstract: Hereditary spastic paraplegia (HSP) is an extremely heterogeneous group of neurodegenerative disorders affecting the longest axons in the central nervous system. The most common genetic form accounting for about 40% of the autosomal-dominant HSP (ADHSP) cases is spastin gene, SPG4. We performed mutation screening of the spastin gene on 36 unrelated HSP patients from three different ethnic groups (Bulgarian, Turks and Gypsies) and found four new mutations and one already reported. The phenotype-genotype correlations in Bulgarian SPG4 patients showed a great difference in the age at disease onset between patients with missense mutations and those harboring deletions and splice-site mutations. Our study is the first to present corroborative clinical data in favor of the general hypothesis that the clinical course of the disease is related to the type of the spastin mutation. The clinical and genealogical findings in Bulgarian SPG4 patients suggest that a positive family history for inheritance as an autosomal-dominant trait is a strong indication for spastin mutation screening.
authors.affiliation: Department of Chemistry and Biochemistry, Medical University, Sofia, Bulgaria. nevy@mail.bg
authors.forename: N
authors.initials: N
authors.lastname: Ivanova
authors.forename: A
authors.initials: A
authors.lastname: Löfgren
authors.forename: I
authors.initials: I
authors.lastname: Tournev
authors.forename: R
authors.initials: R
authors.lastname: Rousev
authors.forename: A
authors.initials: A
authors.lastname: Andreeva
authors.forename: A
authors.initials: A
authors.lastname: Jordanova
authors.forename: V
authors.initials: V
authors.lastname: Georgieva
authors.forename: T
authors.initials: T
authors.lastname: Deconinck
authors.forename: V
authors.initials: V
authors.lastname: Timmerman
authors.forename: I
authors.initials: I
authors.lastname: Kremensky
authors.forename: P
authors.initials: P
authors.lastname: De Jonghe
authors.forename: V
authors.initials: V
authors.lastname: Mitev
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D017668:Age of Onset; D002031:Bulgaria; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000208:ethnology / Q000235:genetics*; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human