title: Defining neurodegeneration on Guam by targeted genomic sequencing.
abstract: OBJECTIVE
  Amyotrophic lateral sclerosis/parkinsonism-dementia complex has been described in Guam, Western Papua, and the Kii Peninsula of Japan. The etiology and pathogenesis of this complex neurodegenerative disease remains enigmatic.
  
  
  METHODS
  In this study, we have used targeted genomic sequencing to evaluate the contribution of genetic variability in the pathogenesis of amyotrophic lateral sclerosis, parkinsonism, and dementia in Guamanian Chamorros.
  
  
  RESULTS
  Genes previously linked to or associated with amyotrophic lateral sclerosis, parkinsonism, dementia, and related neurodegenerative syndromes were sequenced in Chamorro subjects living in the Mariana Islands. Homozygous PINK1 p.L347P, heterozygous DCTN1 p.T54I, FUS p.P431L, and HTT (42 CAG repeats) were identified as pathogenic mutations.
  
  
  CONCLUSIONS
  The findings explain the clinical, pathologic, and genetic heterogeneity observed in some multi-incident families and contribute to the excess incidence of neurodegeneration previously reported on Guam.
authors.affiliation: Micronesian Health Study II, Tamuning, Guam.
authors.forename: John C
authors.initials: JC
authors.lastname: Steele
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guella
authors.forename: Chelsea
authors.initials: C
authors.lastname: Szu-Tu
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Lin
authors.forename: Christina
authors.initials: C
authors.lastname: Thompson
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Evans
authors.forename: Holly E
authors.initials: HE
authors.lastname: Sherman
authors.forename: Carles
authors.initials: C
authors.lastname: Vilariño-Güell
authors.forename: Katrina
authors.initials: K
authors.lastname: Gwinn
authors.forename: Huw
authors.initials: H
authors.lastname: Morris
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics*; D003704:Dementia / Q000453:epidemiology / Q000235:genetics*; D000072159:Dynactin Complex; D006141:Guam / Q000453:epidemiology; D006801:Humans; D000071058:Huntingtin Protein; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D011494:Protein Kinases / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D013577:Syndrome; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000072159:Dynactin Complex; D000071058:Huntingtin Protein; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D011494:Protein Kinases; D034702:RNA-Binding Protein FUS; D000099202:PTEN-Induced Putative Kinase; C000606360:DCTN1 protein, human; C086055:HTT protein, human