title: Analyses of the MAPT, PGRN, and C9orf72 mutations in Japanese patients with FTLD, PSP, and CBS.
abstract: 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 novo 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.
  
  
  CONCLUSIONS
  MAPT p.S285R is the first reported de novo 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.
authors: Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan.
authors: Kotaro
authors: K
authors: Ogaki
authors: Yuanzhe
authors: Y
authors: Li
authors: Masashi
authors: M
authors: Takanashi
authors: Kei-Ichi
authors: K
authors: Ishikawa
authors: Tomonori
authors: T
authors: Kobayashi
authors: Takashi
authors: T
authors: Nonaka
authors: Masato
authors: M
authors: Hasegawa
authors: Masahiko
authors: M
authors: Kishi
authors: Hiroyo
authors: H
authors: Yoshino
authors: Manabu
authors: M
authors: Funayama
authors: Tetsuro
authors: T
authors: Tsukamoto
authors: Keiichi
authors: K
authors: Shioya
authors: Masayuki
authors: M
authors: Yokochi
authors: Hisamasa
authors: H
authors: Imai
authors: Ryogen
authors: R
authors: Sasaki
authors: Yasumasa
authors: Y
authors: Kokubo
authors: Shigeki
authors: S
authors: Kuzuhara
authors: Yumiko
authors: Y
authors: Motoi
authors: Hiroyuki
authors: H
authors: Tomiyama
authors: Nobutaka
authors: N
authors: Hattori
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics; D044466:Asian People; D000073885:C9orf72 Protein; D003598:Cytoskeletal Proteins / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D003704:Dementia / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D005133:Eye Movements / Q000235:genetics; D057174:Frontotemporal Lobar Degeneration / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D000077153:Progranulins; D011506:Proteins / Q000235:genetics*; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D003598:Cytoskeletal Proteins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D011506:Proteins; D016875:tau Proteins