Objective: To report a Parkinson’s disease (PD) patient with homozygous and heterozygous copy number variations of Parkin gene, showing greatly improvement in freezing of gait (FOG) after STN-DBS.

Background: The molecular diagnosis of sporadic Parkinson’s disease is very important, in order to get precise and timely treatment, especially those with early-onset age and complexed motor complications. Patients with copy number variations of Parkin gene are commonly seen in early-onset PD, and usually show more severe clinical manifestations than simple sequence mutations. FOG is poorly controlled in PD patients and greatly affect the quality of daily life. Although Deep Brain Stimulation has been widely used, the improvement of FOG is still an obstacle need to overcome.

Method: Targeted gene capture sequencing and multiplex Ligation-dependent Probe Amplification（MLPA）was performed to confirm the genotype of the patient. Clinical features were carefully evaluated and recorded before and after the STN-DBS surgery.

Results: A 60-year old man was referred to our clinic, complaining of bradykinesia and gait disorders for 15 years. The diagnosis of Parkinson’s disease was finally established. Levodopa and dopamine agonist agents were used and responded well at first. However, the patient developed obvious motor complications and FOG soon. Due to the early onset of age and rapid progression of motor fluctuations, we conducted gene detection to confirm the genotype, showing that the patient had dosage variations in Parkin gene (homozygous deletion in Exon4; and heterozygous deletions in Exon 2,3,5,6). Finally, the patient received the bilateral STN-DBS surgery one year ago. Low frequency and interleaving stimulation were implemented and the clinical manifestations improved greatly, especially the FOG. Although the patient still suffered from motor fluctuations, he showed great satisfaction about the STN-DBS treatment.

Conclusion: Parkinson’s disease patient, with copy number variations in Parkin gene, may show severe motor complications and freezing of gait. The effects of levodopa and dopamine agonist agents are usually limited as the disease progresses. The bilateral STN-DBS may be a satisfactory therapeutic strategy, and low frequency and interleaving stimulation can be considered after the surgery.

« Back to 2019 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-from-genotype-to-phenotype-improvement-in-freezing-of-gait-after-subthalamic-deep-brain-stimulation-stn-dbs-in-a-parkinsons-disease-patient-with-copy-number-variations-of-parkin-g/