Parkinson's Disease with a Novel OPA1 Mutation Successfully Treated with Deep Brain Stimulation

This is the authors' abstract. We don't add key points for this paper.

Mitochondrial dysfunction is crucial in Parkinson ’ s disease (PD) pathogenesis, 1 and mutations in several nuclear-encoded mitochondrial genes cause familial PD. 2 OPA1 , a dynamin-like GTPase of the inner mitochondrial membrane, regulates mitochondrial fusion, cristae remodeling, mtDNA integrity, and respiratory chain assembly. 3 Pathogenic variants cause autosomal dominant optic atrophy (ADOA), isolated or within a multi-system “ ADOA-plus ” syndrome. 4 A few OPA1 -related PD/parkinsonism cases have also been reported. 5,6 We herein describe a case of OPA1 -related PD successfully treated with subthalamic deep brain stimulation (STN-DBS). A 53-year-old woman with a maternal family history of PD (grandmother) presented in 2013 with left-sided bradykinesia and rigidity. Non-motor symptoms included hyposmia, dysgeusia, and mild anxiety. She was diagnosed with PD and started on rotigotine. Levodopa was added in 2016 and variably combined with dopamine agonists, MAO-B and COMT inhibitors. By 2022, she developed motor fl uctuations, including wearing-off with freezing of gait (FOG) at initiation and turn-ings, peak-dose dyskinesias and nocturnal hypokinesia. Clinical exome sequencing and an in-silico parkinsonism-related gene panel revealed OPA1 c.960_963del, p.(Asp321CysfsTer41), a frameshift in exon 10 predicted to truncate the protein. Per ACMG guidelines, this null variant in