title: Phenotype of autosomal dominant spastic paraplegia linked to chromosome 2.
abstract: We report the clinical features of 12 families with autosomal dominant spastic paraplegia (ADSP) linked to the SPG4 locus on chromosome 2p, the major locus for this disorder that accounts for approximately 40% of the families. Among 93 gene carriers, 32 (34%) were unaware of symptoms but were clinically affected. Haplotype reconstruction showed that 90% of the asymptomatic gene carriers presented increased reflexes and/or extensor plantar responses independent of age at examination. The mean age at onset was 29 years, ranging from 1 to 63 years. Intra- as well as inter-familial variability of age at onset was important, but did not result from anticipation. Phenotype-genotype correlations and comparison with SPG3 and SPG5 families indicated that despite the variability of age at onset, SPG4 is a single genetic entity but no clinical features distinguish individual SPG4 patients from those with SPG3 or SPG5 mutations.
authors.affiliation: INSERM U289, Hôpital de la Salpêtrière, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Dürr
authors.forename: C S
authors.initials: CS
authors.lastname: Davoine
authors.forename: C
authors.initials: C
authors.lastname: Paternotte
authors.forename: J
authors.initials: J
authors.lastname: von Fellenberg
authors.forename: S
authors.initials: S
authors.lastname: Cogilinicean
authors.forename: P
authors.initials: P
authors.lastname: Coutinho
authors.forename: C
authors.initials: C
authors.lastname: Lamy
authors.forename: S
authors.initials: S
authors.lastname: Bourgeois
authors.forename: J F
authors.initials: JF
authors.lastname: Prud'homme
authors.forename: C
authors.initials: C
authors.lastname: Penet
authors.forename: J L
authors.initials: JL
authors.lastname: Mas
authors.forename: J M
authors.initials: JM
authors.lastname: Burgunder
authors.forename: J
authors.initials: J
authors.lastname: Hazan
authors.forename: J
authors.initials: J
authors.lastname: Weissenbach
authors.forename: A
authors.initials: A
authors.lastname: Brice
authors.forename: B
authors.initials: B
authors.lastname: Fontaine
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D010264:Paraplegia / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype