title: Identification of a Japanese family with LRRK2 p.R1441G-related Parkinson's disease.
abstract: Leucine-rich repeat kinase 2 (LRRK2) is a causative gene of autosomal dominant familial Parkinson's disease (PD). We screened for LRRK2 mutations in 3 frequently reported exons (31, 41, and 48) in our cohort of 871 Japanese patients with PD (430 with sporadic PD and 441 probands with familial PD). Direct sequencing analysis of LRRK2 revealed 1 proband (0.11%) with a p.R1441G mutation, identified for the first time in Asian countries, besides frequently reported substitutions including, the p.G2019S mutation (0.11%) and p.G2385R variant (11.37%). Several studies have suggested that the LRRK2 p.R1441G mutation, which is highly prevalent in the Basque country, is extremely rare outside of northern Spain. Further analysis of family members of the proband with the p.R1441G mutation revealed that her mother and first cousin shared the same mutation and parkinsonism. Haplotype analysis revealed a different haplotype from that of the original Spanish families. Our patients demonstrated levodopa-responsive parkinsonism with intrafamilial clinical heterogeneity. This is the first report of familial PD because of the LRRK2 p.R1441G mutation in Asia.
authors: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. Electronic address: thatano@juntendo.ac.jp.
authors: Taku
authors: T
authors: Hatano
authors: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Manabu
authors: M
authors: Funayama
authors: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors: Shin-Ichiro
authors: SI
authors: Kubo
authors: Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Department of Neurology, University of Washington, Seattle, WA, USA.
authors: Ignacio F
authors: IF
authors: Mata
authors: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors: Yutaka
authors: Y
authors: Oji
authors: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors: Akio
authors: A
authors: Mori
authors: Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Department of Neurology, University of Washington, Seattle, WA, USA.
authors: Cyrus P
authors: CP
authors: Zabetian
authors: Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Department of Neurology, University of Washington, Seattle, WA, USA.
authors: Sarah M
authors: SM
authors: Waldherr
authors: Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Hiroyo
authors: H
authors: Yoshino
authors: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors: Genko
authors: G
authors: Oyama
authors: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; Department of Research and Therapeutics for Movement Disorders, Juntendo University School of Medicine, Tokyo, Japan.
authors: Yasushi
authors: Y
authors: Shimo
authors: Jichi-idai Station Brain Clinic, Tochigi, Japan.
authors: Ken-Ichi
authors: KI
authors: Fujimoto
authors: Department of Neuropsychiatry, Fukushima Medical University, Fukushima, Japan.
authors: Hirokazu
authors: H
authors: Oshima
authors: Department of Neuropsychiatry, Fukushima Medical University, Fukushima, Japan.
authors: Yasuto
authors: Y
authors: Kunii
authors: Department of Neuropsychiatry, Fukushima Medical University, Fukushima, Japan.
authors: Hirooki
authors: H
authors: Yabe
authors: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors: Yoshikuni
authors: Y
authors: Mizuno
authors: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: nhattori@juntendo.ac.jp.
authors: Nobutaka
authors: N
authors: Hattori
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics*; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D007980:Levodopa; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: Asia; Intrafamilial clinical heterogeneity; LRRK2; Parkinson's disease; p.R1441G