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Genetic linkage of autosomal dominant progressive supranuclear palsy to 1q31.1
Author(s) -
Ros Raquel,
Gómez Garre Pilar,
Hirano Michio,
Tai Yen F.,
Ampuero Israel,
Vidal Lídice,
Rojo Ana,
Fontan Aurora,
Vazquez Ana,
Fanjul Samira,
Hernandez Jaime,
Cantarero Susana,
Hoenicka Janet,
Jones Alison,
Ahsan R. Laila,
Pavese Nicola,
Piccini Paola,
Brooks David J.,
PerezTur Jordi,
Nyggard Torbjorn,
de Yébenes Justo G.
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20449
Subject(s) - progressive supranuclear palsy , genetic linkage , neuropathology , genetics , locus (genetics) , pathogenesis , chromosome , disease , biology , gene , medicine , pathology , atrophy
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 18 F‐fluoro‐dopa and 18 F‐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 3.4cM 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. Ann Neurol 2005;57:634–641