title: The S18Y polymorphism in the UCHL1 gene is a genetic modifier in Huntington's disease.
abstract: An expanded polyglutamine stretch in the huntingtin protein has been identified as the pathogenetic cause of Huntington's disease (HD). Although the length of the expanded polyglutamine repeat is inversely correlated with the age-at-onset, additional genetic factors are thought to modify the variance in the disease onset. As linkage analysis suggested a modifier locus on chromosome 4p, we investigated the functional relevance of S18Y polymorphism of the ubiquitin carboxy-terminal hydrolase L1 in 946 Caucasian HD patients. In this group, the allelic variation on locus S18Y is responsible for 1.1% of the variance in the HD age-at-onset, and the rare Y allele is associated with younger-aged cases.
authors.affiliation: Department of Medical Genetics, University of Tübingen, Calwerstrasse 7, 72076 Tübingen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Metzger
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.forename: Juergen
authors.initials: J
authors.lastname: Tomiuk
authors.forename: Franco
authors.initials: F
authors.lastname: Laccone
authors.forename: Stefano
authors.initials: S
authors.lastname: Didonato
authors.forename: Cinzia
authors.initials: C
authors.lastname: Gellera
authors.forename: Paola
authors.initials: P
authors.lastname: Soliveri
authors.forename: Herwig W
authors.initials: HW
authors.lastname: Lange
authors.forename: Helga
authors.initials: H
authors.lastname: Weirich-Schwaiger
authors.forename: Gregor K
authors.initials: GK
authors.lastname: Wenning
authors.forename: Bela
authors.initials: B
authors.lastname: Melegh
authors.forename: Victoria
authors.initials: V
authors.lastname: Havasi
authors.forename: Lazlo
authors.initials: L
authors.lastname: Balikó
authors.forename: Stefan
authors.initials: S
authors.lastname: Wieczorek
authors.forename: Larissa
authors.initials: L
authors.lastname: Arning
authors.forename: Jacek
authors.initials: J
authors.lastname: Zaremba
authors.forename: Anna
authors.initials: A
authors.lastname: Sulek
authors.forename: Dorota
authors.initials: D
authors.lastname: Hoffman-Zacharska
authors.forename: A Nazli
authors.initials: AN
authors.lastname: Basak
authors.forename: Nagehan
authors.initials: N
authors.lastname: Ersoy
authors.forename: Jana
authors.initials: J
authors.lastname: Zidovska
authors.forename: Vera
authors.initials: V
authors.lastname: Kebrdlova
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
authors.forename: Pascale
authors.initials: P
authors.lastname: Ribaï
authors.forename: Ludovit
authors.initials: L
authors.lastname: Kadasi
authors.forename: Marta
authors.initials: M
authors.lastname: Kvasnicova
authors.forename: Bernhard H F
authors.initials: BH
authors.lastname: Weber
authors.forename: Friedmar
authors.initials: F
authors.lastname: Kreuz
authors.forename: Matthias
authors.initials: M
authors.lastname: Dose
authors.forename: Manfred
authors.initials: M
authors.lastname: Stuhrmann
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
mesh_terms: D017668:Age of Onset; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D018911:Trinucleotide Repeats; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase