title: Genetic linkage of autosomal dominant progressive supranuclear palsy to 1q31.1.
abstract: Progressive supranuclear palsy (PSP) is a disorder of unknown pathogenesis. Familial clusters of PSP have been reported related to mutations of protein tau. We report the linkage of a large Spanish family with typical autosomal dominant PSP to a new locus in chromosome 1. Four members of this family had typical PSP, confirmed by neuropathology in one case. At least five ancestors had similar disease. Other members of the family have incomplete phenotypes. The power of the linkage analysis was increased by detecting presymptomatic individuals with 18F-fluoro-dopa and 18F-deoxyglucose positron emission tomography. We screened the human genome with 340 polymorphic markers and we enriched the areas of interest with additional markers. The disease status was defined according to the clinical and positron emission tomography data. We excluded linkage to the tau gene in chromosome 17. PSP was linked, in this family, to one area of 3.4 cM in chromosome 1q31.1, with a maximal multipoint < OD score of +3.53. This area contains at least three genes, whose relevance in PSP is unknown. We expect to further define the gene responsible for PSP, which could help to understand the pathogenesis of this disease and to design effective treatment.
authors.affiliation: Banco de Tejidos para Investigaciones Neurológicas, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Ros
authors.forename: Pilar
authors.initials: P
authors.lastname: Gómez Garre
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Yen F
authors.initials: YF
authors.lastname: Tai
authors.forename: Israel
authors.initials: I
authors.lastname: Ampuero
authors.forename: Lídice
authors.initials: L
authors.lastname: Vidal
authors.forename: Ana
authors.initials: A
authors.lastname: Rojo
authors.forename: Aurora
authors.initials: A
authors.lastname: Fontan
authors.forename: Ana
authors.initials: A
authors.lastname: Vazquez
authors.forename: Samira
authors.initials: S
authors.lastname: Fanjul
authors.forename: Jaime
authors.initials: J
authors.lastname: Hernandez
authors.forename: Susana
authors.initials: S
authors.lastname: Cantarero
authors.forename: Janet
authors.initials: J
authors.lastname: Hoenicka
authors.forename: Alison
authors.initials: A
authors.lastname: Jones
authors.forename: R Laila
authors.initials: RL
authors.lastname: Ahsan
authors.forename: Nicola
authors.initials: N
authors.lastname: Pavese
authors.forename: Paola
authors.initials: P
authors.lastname: Piccini
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Jordi
authors.initials: J
authors.lastname: Perez-Tur
authors.forename: Torbjorn
authors.initials: T
authors.lastname: Nyggard
authors.forename: Justo G
authors.initials: JG
authors.lastname: de Yébenes
mesh_terms: D000368:Aged; D001923:Brain Chemistry / Q000502:physiology; D002421:Caudate Nucleus / Q000000981:diagnostic imaging; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging; D019275:Radiopharmaceuticals; D013494:Supranuclear Palsy, Progressive / Q000000981:diagnostic imaging / Q000235:genetics*
chemical_list: D019275:Radiopharmaceuticals; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004247:DNA; D005947:Glucose