Clinicogenetic study of mutations in LRRK2 exon 41 in Parkinsons's disease patients from 18 countries

Hiroyuki Tomiyama, Yuanzhe Li, Manabu Funayama, Kazuko Hasegawa, Hiroyo Yoshino, Shin Ichiro Kubo, Kenichi Sato, Tatsuya Hattori, Chin Song Lu, Rivka Inzelberg, Ruth Djaldetti, Eldad Melamed, Rim Amouri, Neziha Gouider-Khouja, Faycal Hentati, Yasuko Hatano, Mei Wang, Yoko Imamichi, Koichi Mizoguchi, Hiroaki MiyajimaFumiya Obata, Tatsushi Toda, Matthew J. Farrer, Yoshikuni Mizuno, Nobutaka Hattori*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

105 Scopus citations


We screened LRRK2 mutations in exon 41 in 904 parkin-negative Parkinson's disease (PD) patients (868 pro-bands) 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 123I-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.

Original languageEnglish
Pages (from-to)1102-1108
Number of pages7
JournalMovement Disorders
Issue number8
StatePublished - 08 2006
Externally publishedYes


  • Cardiac l-metaiodobenzylguanidine (MIBG) scintigraphy
  • Genetics
  • Leucinrich repeat kinase 2 (LRRK2)
  • PARK8
  • Parkinson's disease


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