1. Defining neurodegeneration on Guam by targeted genomic sequencing.
- Author
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Steele JC, Guella I, Szu-Tu C, Lin MK, Thompson C, Evans DM, Sherman HE, Vilariño-Güell C, Gwinn K, Morris H, Dickson DW, and Farrer MJ
- Subjects
- Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis epidemiology, Dementia epidemiology, Dynactin Complex, Guam epidemiology, Humans, Huntingtin Protein, Male, Middle Aged, Parkinson Disease epidemiology, Pedigree, Syndrome, Amyotrophic Lateral Sclerosis genetics, Dementia genetics, Microtubule-Associated Proteins genetics, Nerve Tissue Proteins genetics, Parkinson Disease genetics, Protein Kinases genetics, RNA-Binding Protein FUS genetics
- 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., 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., (© 2015 American Neurological Association.)
- Published
- 2015
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