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. 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.

journal_name

Ann Neurol

journal_title

Annals of neurology

authors

Steele JC,Guella I,Szu-Tu C,Lin MK,Thompson C,Evans DM,Sherman HE,Vilariño-Güell C,Gwinn K,Morris H,Dickson DW,Farrer MJ

doi

10.1002/ana.24346

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

458-68

issue

3

eissn

0364-5134

issn

1531-8249

journal_volume

77

pub_type

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