title: Spastic paraplegia 5: Locus refinement, candidate gene analysis and clinical description.
abstract: Thirty-three different loci for hereditary spastic paraplegias (HSP) have been mapped, and 15 responsible genes have been identified. Autosomal recessive spastic paraplegias (ARHSPs) usually have clinically complex phenotypes but the SPG5, SPG24, and SPG28 loci are considered to be associated with pure forms of the disease. We performed a genome-wide scan in a large French family. Fine mapping of the refined SPG5 region on chromosome 8q12 was performed in another 17 ARHSP families with additional microsatellite markers. After exclusion of known ARHSP loci, the genome-wide screen provided evidence of linkage with a maximal multipoint lod score of 2.6 in the D8S1113-D8S1699 interval. This interval partially overlapped SPG5 and reduced it to a 5.9 megabase (Mb)-region between D8S1113 and D8S544. In a family of Algerian origin from a series of 17 other ARHSP kindreds, linkage to the SPG5 locus was supported by a multipoint lod score of 2.3. The direct sequencing of the coding exons of seven candidate genes did not detect mutations/polymorphisms in the index cases of both linked families. The phenotype of the two SPG5-linked families consisted of spastic paraparesis associated with deep sensory loss. In several patients with long disease durations, there were also mild cerebellar signs. The frequency of SPG5 was approximately 10% (2/18) in our series of ARHSP families with pure or complex forms. We have refined the SPG5 locus to a 3.8 cM interval and extended the phenotype of this form of ARHSP to include slight cerebellar signs.
authors.affiliation: INSERM U679, Pierre and Marie Curie Paris 6 University, Pitié-Salpêtrière Hospital, 47 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.
authors.forename: Stephan
authors.initials: S
authors.lastname: Klebe
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Naima
authors.initials: N
authors.lastname: Bouslam
authors.forename: Djamel
authors.initials: D
authors.lastname: Grid
authors.forename: Caroline
authors.initials: C
authors.lastname: Paternotte
authors.forename: Christel
authors.initials: C
authors.lastname: Depienne
authors.forename: Sylvain
authors.initials: S
authors.lastname: Hanein
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bouhouche
authors.forename: Nizar
authors.initials: N
authors.lastname: Elleuch
authors.forename: Hamid
authors.initials: H
authors.lastname: Azzedine
authors.forename: Sandrine
authors.initials: S
authors.lastname: Poea-Guyon
authors.forename: Sylvie
authors.initials: S
authors.lastname: Forlani
authors.forename: Elodie
authors.initials: E
authors.lastname: Denis
authors.forename: Céline
authors.initials: C
authors.lastname: Charon
authors.forename: Jamile
authors.initials: J
authors.lastname: Hazan
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
mesh_terms: D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D005192:Family Health; D005808:Genes, Recessive; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D018895:Microsatellite Repeats; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis / Q000235:genetics*