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Clinicogenetic study of mutations in LRRK2 exon 41 in Parkinson's disease patients from 18 countries
Author(s) -
Tomiyama Hiroyuki,
Li Yuanzhe,
Funayama Manabu,
Hasegawa Kazuko,
Yoshino Hiroyo,
Kubo ShinIchiro,
Sato Kenichi,
Hattori Tatsuya,
Lu ChinSong,
Inzelberg Rivka,
Djaldetti Ruth,
Melamed Eldad,
Amouri Rim,
GouiderKhouja Neziha,
Hentati Faycal,
Hatano Yasuko,
Wang Mei,
Imamichi Yoko,
Mizoguchi Koichi,
Miyajima Hiroaki,
Obata Fumiya,
Toda Tatsushi,
Farrer Matthew J.,
Mizuno Yoshikuni,
Hattori Nobutaka
Publication year - 2006
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.20886
Subject(s) - lrrk2 , proband , missense mutation , exon , mutation , neuropathology , dementia , medicine , genetics , parkin , frontotemporal dementia , disease , biology , parkinson's disease , gene
We screened LRRK2 mutations in exon 41 in 904 parkin ‐negative Parkinson's disease (PD) patients (868 probands) from 18 countries across 5 continents. We found three heterozygous missense (novel I2012T, G2019S, and I2020T) mutations in LRRK2 exon 41. We identified 11 (1.3%) among 868 PD probands, including 2 sporadic cases and 8 (6.2%) of 130 autosomal dominant PD families. The LRRK2 mutations in exon 41 exhibited relatively common and worldwide distribution. Among the three mutations in exon 41, it has been reported that Caucasian patients with G2019S mutation have a single‐founder effect. In the present study, Japanese patients with G2019S were unlikely to have a single founder from the Caucasian patients. In contrast, I2020T mutation has a single‐founder effect in Japanese patients. Clinically, patients with LRRK2 mutations had typical idiopathic PD. Notably, several patients developed dementia and psychosis, and one with I2020T had low cardiac 123 I‐metaiodobenzylguanidine (MIBG) heart/mediastinum ratio, although the ratio was not low in other patients with I2020T or G2019S. Clinical phenotypes including psychosis, dementia, and MIBG ratios are also heterogeneous, similar to neuropathology, in PD associated with LRRK2 mutations. © 2006 Movement Disorder Society