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.
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.
Authors: Takuya Konno; Owen A Ross; Hélio A G Teive; Jarosław Sławek; Dennis W Dickson; Zbigniew K Wszolek Journal: Parkinsonism Relat Disord Date: 2017-06-12 Impact factor: 4.891
Authors: Maya L Lichtenstein; Emily Dwosh; Anupama Roy Chowdhury; Matthew J Farrer; Marna B McKenzie; Ilaria Guella; Daniel M Evans; Haakon B Nygaard; Jason R Shewchuk; Sherri Hayden; Jason J S Barton; Howard H Feldman Journal: Neurol Clin Pract Date: 2017-10
Authors: Ilaria Guella; Linda Huh; Marna B McKenzie; Eric B Toyota; E Martina Bebin; Michelle L Thompson; Gregory M Cooper; Daniel M Evans; Sarah E Buerki; Shelin Adam; Margot I Van Allen; Tanya N Nelson; Mary B Connolly; Matthew J Farrer; Michelle Demos Journal: Neurol Genet Date: 2016-11-10