Genetic linkage of autosomal dominant progressive supranuclear palsy to 1q31.1.
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.
Ros
Raquel
R
Banco de Tejidos para Investigaciones Neurológicas, Madrid, Spain.
Gómez Garre
Pilar
P
Hirano
Michio
M
Tai
Yen F
YF
Ampuero
Israel
I
Vidal
Lídice
L
Rojo
Ana
A
Fontan
Aurora
A
Vazquez
Ana
A
Fanjul
Samira
S
Hernandez
Jaime
J
Cantarero
Susana
S
Hoenicka
Janet
J
Jones
Alison
A
Ahsan
R Laila
RL
Pavese
Nicola
N
Piccini
Paola
P
Brooks
David J
DJ
Perez-Tur
Jordi
J
Nyggard
Torbjorn
T
de Yébenes
Justo G
JG
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*
D019275:Radiopharmaceuticals; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004247:DNA; D005947:Glucose