title: Seven novel mutations and four exon deletions in a collection of Norwegian patients with SPG4 hereditary spastic paraplegia.
abstract: To establish the phenotypic variation and frequency of SPAST mutations or deletions in Norwegian patients with hereditary spastic paraplegia (HSP), we examined 59 unrelated patients with HSP and screened for DNA point mutations and microdeletions in SPG4. Forty-one had a familial history, 35 had a clear dominant inheritance, six had other affected sibs and 18 were sporadic. We found 12 mutations in SPG4, seven of them novel, and four different heterozygous exon deletions, two of them novel. Mutations were found in 16 families showing autosomal dominant (AD) inheritance, and in one sporadic case. In two non-SPG4 families the S44L polymorphism/modifier was found in both affected and unaffected individuals. This is the first study of Norwegian patients with HSP since the 1970s, and the first report on SPG4 in Norway. Our results show that SPG4 mutations and deletions are a significant cause of HSP in our population and warrant SPG4 screening in AD families and selected sporadic cases.
authors.affiliation: Department of Neurology, Ullevål University Hospital, Oslo, Norway. anhs@uus.no
authors.forename: A K
authors.initials: AK
authors.lastname: Erichsen
authors.forename: E
authors.initials: E
authors.lastname: Inderhaug
authors.forename: M
authors.initials: M
authors.lastname: Mattingsdal
authors.forename: K
authors.initials: K
authors.lastname: Eiklid
authors.forename: C M E
authors.initials: CM
authors.lastname: Tallaksen
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000502:physiology; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009664:Norway / Q000453:epidemiology; D010641:Phenotype; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D017384:Sequence Deletion; D015419:Spastic Paraplegia, Hereditary / Q000453:epidemiology / Q000235:genetics*; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human