The S18Y polymorphism in the UCHL1 gene is a genetic modifier in Huntington's disease.
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.
Metzger
Silke
S
Department of Medical Genetics, University of Tübingen, Calwerstrasse 7, 72076 Tübingen, Germany.
Bauer
Peter
P
Tomiuk
Juergen
J
Laccone
Franco
F
Didonato
Stefano
S
Gellera
Cinzia
C
Soliveri
Paola
P
Lange
Herwig W
HW
Weirich-Schwaiger
Helga
H
Wenning
Gregor K
GK
Melegh
Bela
B
Havasi
Victoria
V
Balikó
Lazlo
L
Wieczorek
Stefan
S
Arning
Larissa
L
Zaremba
Jacek
J
Sulek
Anna
A
Hoffman-Zacharska
Dorota
D
Basak
A Nazli
AN
Ersoy
Nagehan
N
Zidovska
Jana
J
Kebrdlova
Vera
V
Pandolfo
Massimo
M
Ribaï
Pascale
P
Kadasi
Ludovit
L
Kvasnicova
Marta
M
Weber
Bernhard H F
BH
Kreuz
Friedmar
F
Dose
Matthias
M
Stuhrmann
Manfred
M
Riess
Olaf
O
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*
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase