A novel homozygous SYNJ1 mutation in two siblings with typical Parkinson's disease

Background: Mutations in the SYNJ1 have been associated with early onset of atypical Parkinson's disease (PARK20). Patients with PARK20 exhibit a wide phenotypic variability. Here, we report the clinical and genetic findings in two affected siblings with a novel homozygous SYNJ1 mutation.

Methods: A consanguineous family with two affected siblings with Parkinson's disease was recruited. Both siblings underwent detailed neurological examinations. Whole genome sequencing was performed in the proband.

Results: Both affected siblings presented with pure parkinsonism with no other atypical symptoms and a slow disease progression. The proband had an excellent response to levodopa. Performing the levodopa challenge test in the proband's older brother resulted in improvements in the parkinsonism signs. Genetic analysis identified a homozygous missense mutation in SYNJ1 (c.2495A > G, p.Y832C) in both of siblings. In silico analyses revealed that the mutation was deleterious.

Conclusions: Screening for SNYJ1 should be considered in patients with typical levodopa-responsive Parkinson's disease.