title: Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia.
abstract: Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by pro- gressive spasticity of the lower limbs. Five AD-HSP loci have been mapped to chromosomes 14q, 2p, 15q, 8q and 12q. The SPG4 locus at 2p21-p22 has been shown to account for approximately 40% of all AD-HSP families. SPG4 encoding spastin, a putative nuclear AAA protein, has recently been identified. Here, sequence analysis of the 17 exons of SPG4 in 87 unrelated AD-HSP patients has resulted in the detection of 34 novel mutations. These SPG4 mutations are scattered along the coding region of the gene and include all types of DNA modification including missense (28%), nonsense (15%) and splice site point (26.5%) mutations as well as deletions (23%) and insertions (7.5%). The clinical analysis of the 238 mutation carriers revealed a high proportion of both asymptomatic carriers (14/238) and patients unaware of symptoms (45/238), and permitted the redefinition of this frequent form of AD-HSP.
authors.affiliation: Genoscope, 2 rue Gaston Crémieux, 91000 Evry, France.
authors.forename: N
authors.initials: N
authors.lastname: Fonknechten
authors.forename: D
authors.initials: D
authors.lastname: Mavel
authors.forename: P
authors.initials: P
authors.lastname: Byrne
authors.forename: C S
authors.initials: CS
authors.lastname: Davoine
authors.forename: C
authors.initials: C
authors.lastname: Cruaud
authors.forename: D
authors.initials: D
authors.lastname: Bönsch
authors.forename: D
authors.initials: D
authors.lastname: Boentsch
authors.forename: D
authors.initials: D
authors.lastname: Samson
authors.forename: P
authors.initials: P
authors.lastname: Coutinho
authors.forename: M
authors.initials: M
authors.lastname: Hutchinson
authors.forename: P
authors.initials: P
authors.lastname: McMonagle
authors.forename: J M
authors.initials: JM
authors.lastname: Burgunder
authors.forename: A
authors.initials: A
authors.lastname: Tartaglione
authors.forename: O
authors.initials: O
authors.lastname: Heinzlef
authors.forename: I
authors.initials: I
authors.lastname: Feki
authors.forename: T
authors.initials: T
authors.lastname: Deufel
authors.forename: N
authors.initials: N
authors.lastname: Parfrey
authors.forename: A
authors.initials: A
authors.lastname: Brice
authors.forename: B
authors.initials: B
authors.lastname: Fontaine
authors.forename: J F
authors.initials: JF
authors.lastname: Prud'homme
authors.forename: J
authors.initials: J
authors.lastname: Weissenbach
authors.forename: A
authors.initials: A
authors.lastname: Dürr
authors.forename: J
authors.initials: J
authors.lastname: Hazan
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000502:physiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D018389:Codon, Nonsense; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010264:Paraplegia / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012326:RNA Splicing; D000074181:Spastin
chemical_list: D018389:Codon, Nonsense; D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human