期刊
PARKINSONISM & RELATED DISORDERS
卷 19, 期 1, 页码 15-20出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.parkreldis.2012.06.019
关键词
MAPT; PGRN; C9orf72; De novo; Abnormal eye movements
资金
- Strategic Research Foundation
- Japanese Ministry of Education, Culture, Sports, Science and Technology
- Research Committee of CNS Degenerative Diseases
- Muro Disease (Kii ALS/PDC)
- Research Committee on CNS Degenerative Diseases
- Perry Syndrome from the Ministry of Health, Labor and Welfare of Japan
- Juntendo University School of Medicine
- CREST from the Japan Science and Technology Agency (JST)
Background: Mutations in the microtubule associated protein tau (MAPT) and progranulin (PGRN) have been identified in several neurodegenerative disorders, such as frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). Recently, C9orf72 repeat expansion was reported to cause FTLD and amyotrophic lateral sclerosis (ALS). To date, no comprehensive analyses of mutations in these three genes have been performed in Asian populations. The aim of this study was to investigate the genetic and clinical features of Japanese patients with MAPT, PGRN, or C9orf72 mutations. Methods: MAPT and PGRN were analyzed by direct sequencing and gene dosage assays, and C9orf72 repeat expansion was analyzed by repeat-primed PCR in 75 (48 familial, 27 sporadic) Japanese patients with FTLD, PSP, or CBS. Results: We found four MAPT mutations in six families, one novel PGRN deletion/insertion, and no repeat expansion in C9orf72. Intriguingly, we identified a de nova MAPT p.S285R mutation. All six patients with early-onset PSP and the abnormal eye movements that are not typical of sporadic PSP had MAPT mutations. The gene dosages of MAPT and PGRN were normal. Discussion: MAPT p.S285R is the first reported de nova mutation in a sporadic adult-onset patient. MAPT mutation analysis is recommended in both familial and sporadic patients, especially in early-onset PSP patients with these abnormal eye movements. Although PGRN and C9orf72 mutations were rare in this study, the PGRN mutation was found in this Asian FTLD. These genes should be studied further to improve the clinicogenetic diagnoses of FTLD, PSP, and CBS. (c) 2012 Published by Elsevier Ltd.
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