Detection of ATXN2 Expansions in an Exome Dataset: An Underdiagnosed Cause of Parkinsonism.
Mov Disord Clin Pract
; 10(4): 664-669, 2023 Apr.
Article
in En
| MEDLINE
| ID: mdl-37070044
ABSTRACT
Background:
CAG-repeat expansions in Ataxin 2 (ATXN2) are known to cause spinocerebellar ataxia type 2 (SCA2), but CAA interrupted expansions may also result in autosomal dominant Parkinson's disease (AD PD). However, because of technical limitations, such expansions are not explored in whole exome sequencing (WES) data.Objectives:
To identify ATXN2 expansions using WES data from PD cases.Methods:
We explored WES data from a cohort of 477 index cases with PD using ExpansionHunter (Illumina DRAGEN Bio-IT Platform, San Diego, CA). Putative expansions were confirmed by combining polymerase chain reaction and fragment length analysis followed by sub-cloning and sequencing methods.Results:
Using ExpansionHunter, we identified three patients from two families with AD PD carrying either ATXN2 22/39 or 22/37 repeats, both interrupted by four CAA repeats.Conclusion:
These findings demonstrate the usefulness of WES to detect pathogenic CAG repeat expansions, which were found in 1.7% of AD PD in the ATXN2 gene in our exome dataset.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Diagnostic_studies
/
Prognostic_studies
Language:
En
Journal:
Mov Disord Clin Pract
Year:
2023
Document type:
Article