Defining neurodegeneration on Guam by targeted genomic sequencing

John C. Steele, Ilaria Guella, Chelsea Szu-Tu, Michelle K. Lin, Christina Thompson, Daniel M. Evans, Holly E. Sherman, Carles Vilariño-Güell, Katrina Gwinn, Huw Morris, Dennis W. Dickson, Matthew J. Farrer

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


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. Interpretation: 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.

Original languageEnglish (US)
Pages (from-to)458-468
Number of pages11
JournalAnnals of neurology
Issue number3
StatePublished - Mar 1 2015

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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