Detection of Expansions in an Exome Dataset: An Underdiagnosed Cause of Parkinsonism.

BACKGROUND

CAG-repeat expansions in () 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 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 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 gene in our exome dataset.