Mutation analysis and association studies of the ubiquitin carboxy-terminal hydrolase L1 gene in Huntington's disease.
Huntington's disease (HD) is attributed to a triplet CAG repeat mutation, and about 70% of the variance in age-at-onset can be explained by the size of the repeat expansion. Among potential candidates as modifier genes, we investigated the role of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene. We examined the association of HD with the I93M mutation and S18Y polymorphism in 138 HD patients and 136 control subjects, but we did not identify the I93M mutation. The S18Y polymorphism was present in 17% of HD patients. Of the variance in the age-at-onset that was not accounted for by the CAG repeat, 13% could be attributed to S18Y polymorphism. We sequenced the entire coding region of the UCH-L1 gene in seven HD patients with unexplained older or younger onset age. The S18Y polymorphism was found in three out of the four patients presenting with a later age-at-onset. We conclude that the UCH-L1 gene may be a genetic factor that influences the variability in age-at-onset of HD.
Laboratoire de Biochimie et de Biologie Moléculaire, Unité Fonctionnelle de Neurobiologie, Hôpital R. Salengro, Centre Hospitalier Régional et Universitaire de Lille, 59037 Lille Cedex, France.
Peggy
P
Nazé
Isabelle
I
Vuillaume
Alain
A
Destée
Florence
F
Pasquier
Bernard
B
Sablonnière
D000328:Adult; D017668:Age of Onset; D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006816:Huntington Disease / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D046988:Proteasome Endopeptidase Complex; D013869:Thiolester Hydrolases / Q000172:deficiency* / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D043222:Ubiquitin Thiolesterase
D009097:Multienzyme Complexes; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex