Objective: To report a case of a 65-year-old Korean woman diagnosed with a rare gene mutation involving VPS35 linked to Parkinson’s disease (PD).

Background: Major advances have been made in characterizing genetic factors involved in PD [1]. VPS35 is one of the monogenic autosomal dominant mutations identified with a prevalence of less than 1% in familial PD. Less is known about the epidemiology of this mutation across racial groups, with most cases of VPS35 Asp620Asn mutations reported in White populations [2], and rarely reported in Asians, except for Japanese [3] and one Taiwanese family [4]. VPS35-related Parkinson disease (PARK-VPS35) presents with symptoms of typical PD, with a median age of onset of 50 years.

Method: A case report was prepared after reviewing the chart of a two-year clinical course of this patient.

Results: A 65-year-old Korean woman was referred for evaluation of possible PD with symptoms of left arm and leg stiffness, internal shakiness, and a family history of PD in her mother and maternal grandmother. On physical examination, mild left sided bradykinesia was observed. MRI showed bilateral absent swallow tail sign with T2 bilateral hyperintense foci. A DAT scan confirmed diagnosis of PD with bilateral decreased putamen activity and decreased left caudate activity. The patient was started on carbidopa/levodopa therapy. At a follow-up visit two years later, the patient noted that despite the increased dose of carbidopa/levodopa from BID to TID, the effects wore off leading to tremor and stiffness in the left hand. She also endorsed feeling depressed, but did not have memory deficits. In 2024, the patient’s genetic testing was positive for the VPS35 gene with the aspartic-acid-to-asparagine mutation at residue 620 (p.D620N, c.1858G>A, Asp620Asn).

Conclusion: PARK-VPS35 is a rare genetic mutation that has not been widely characterized in different racial groups. We report a case of PARK-VPS35 in a 65-year-old Korean woman, who presented with symptoms of typical PD. To our knowledge, this is the first reported case of PARK-VPS35 D620N mutation in a patient with Korean ancestry. While PARK-VPS35 is generally highly responsive to levodopa therapy, this patient exhibited progressive sensitization. Further studies should be done to dissect how this mutation manifests in different populations and to better understand its clinical presentation.

References: [1] Lill CM. Genetics of Parkinson’s disease. Molecular and Cellular Probes 2016; 30(6): 386-396.

[2] Vilariño-Güell C, Wider C, Ross OA, Dachsel JC, Kachergus JM, Lincoln SJ, et al. VPS35 Mutations in Parkinson Disease. Am J Hum Genet 2011; 89(1): 162-167.

[3] Ando M, Funayama M, Li Y, Kashihara K, Murakami Y, Ishizu N, et al. VPS35 mutation in Japanese patients with typical Parkinson’s disease. Movement Disorders 2012; 27(11): 1413-1417.

[4] Chen YF, Chang YY, Lan MY, Chen PL, Lin CH. Identification of VPS35 p.D620N mutation-related Parkinson’s disease in a Taiwanese family with successful bilateral subthalamic nucleus deep brain stimulation: a case report and literature review. BMC Neurol 2017; 17(1): 191.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/vps35-related-parkinson-disease-in-a-patient-of-korean-ancestry-a-case-report/