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01-03-2006 | Original Article

The S18Y polymorphism in the UCHL1 gene is a genetic modifier in Huntington’s disease

Authors: Silke Metzger, Peter Bauer, Juergen Tomiuk, Franco Laccone, Stefano Didonato, Cinzia Gellera, Paola Soliveri, Herwig W. Lange, Helga Weirich-Schwaiger, Gregor K. Wenning, Bela Melegh, Victoria Havasi, Lazlo Balikó, Stefan Wieczorek, Larissa Arning, Jacek Zaremba, Anna Sulek, Dorota Hoffman-Zacharska, A. Nazli Basak, Nagehan Ersoy, Jana Zidovska, Vera Kebrdlova, Massimo Pandolfo, Pascale Ribaï, Ludovit Kadasi, Marta Kvasnicova, Bernhard H. F. Weber, Friedmar Kreuz, Matthias Dose, Manfred Stuhrmann, Olaf Riess

Published in: Neurogenetics | Issue 1/2006

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.

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Title: The S18Y polymorphism in the UCHL1 gene is a genetic modifier in Huntington’s disease
Authors: Silke Metzger
Peter Bauer
Juergen Tomiuk
Franco Laccone
Stefano Didonato
Cinzia Gellera
Paola Soliveri
Herwig W. Lange
Helga Weirich-Schwaiger
Gregor K. Wenning
Bela Melegh
Victoria Havasi
Lazlo Balikó
Stefan Wieczorek
Larissa Arning
Jacek Zaremba
Anna Sulek
Dorota Hoffman-Zacharska
A. Nazli Basak
Nagehan Ersoy
Jana Zidovska
Vera Kebrdlova
Massimo Pandolfo
Pascale Ribaï
Ludovit Kadasi
Marta Kvasnicova
Bernhard H. F. Weber
Friedmar Kreuz
Matthias Dose
Manfred Stuhrmann
Olaf Riess
Publication date: 01-03-2006
Publisher: Springer-Verlag
Published in: Neurogenetics / Issue 1/2006
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-005-0023-z

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The S18Y polymorphism in the UCHL1 gene is a genetic modifier in Huntington’s disease

Abstract

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