Molecular epidemiological study of familial amyotrophic lateral sclerosis in Japanese population by whole-exome sequencing and identification of novel HNRNPA1 mutation.
Neurobiol Aging
; 61: 255.e9-255.e16, 2018 01.
Article
in En
| MEDLINE
| ID: mdl-29033165
ABSTRACT
To elucidate the genetic epidemiology of familial amyotrophic lateral sclerosis (FALS) in the Japanese population, we conducted whole-exome sequencing analysis of 30 FALS families in whom causative mutations have not been identified in previous studies. Consequently, whole-exome sequencing analysis revealed novel mutations in HNRNPA1, TBK1, and VCP. Taken together with our previous results of mutational analyses by direct nucleotide sequencing analysis, a microarray-based resequencing method, or repeat-primed PCR analysis, causative mutations were identified in 41 of the 68 families (60.3%) with SOD1 being the most frequent cause of FALS (39.7%). Of the mutations identified in this study, a novel c.862/1018C>G (p.P288A/340A) mutation in HNRNPA1 located in the nuclear localization signal domain of hnRNPA1, enhances the recruitment of mutant hnRNPA1 into stress granules, indicating that an altered nuclear localization signal activity plays an essential role in amyotrophic lateral sclerosis pathogenesis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Asian People
/
Genetic Association Studies
/
Heterogeneous Nuclear Ribonucleoprotein A1
/
Exome Sequencing
/
Amyotrophic Lateral Sclerosis
/
Mutation
Type of study:
Diagnostic_studies
Limits:
Female
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
Neurobiol Aging
Year:
2018
Document type:
Article
Affiliation country:
Japan