DNAJC13 genetic variants in parkinsonism

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• A specific DNAJC13 mutation (p.N855S) is associated with familial, late-onset Lewy body parkinsonism.
• This association was initially observed in a multi-incident kindred of Dutch-German-Russian Mennonite descent.

Purpose of the Study:

• To investigate the role of rare DNAJC13 variants in parkinsonism.
• To identify novel genetic factors contributing to parkinsonism susceptibility.

Main Methods:

• DNAJC13 gene sequencing was performed on 201 Canadian patients with parkinsonism and 194 controls.
• Rare missense variants (minor allele frequency < 0.01) found in patients were genotyped in two Parkinson's disease case-control cohorts.

Main Results:

• Eighteen rare missense mutations in DNAJC13 were identified.
• Eleven of these mutations were found exclusively in patients, while three occurred in both patients and controls.
• Specific variants like p.E1740Q and p.L2170W were more frequent in patients, while p.R1516H was more frequent in controls. Several other variants were identified in individual patients.

Conclusions:

• The contribution of rare genetic variations in DNAJC13 to parkinsonisms requires further investigation.
• Beyond the known p.N855S mutation, other rare DNAJC13 variants may play a role in parkinsonism susceptibility.