Objective: The aim of our study is to describe the clinical features and genetic profile of patients of PARK-PINK1 and to draw correlation with genetic variants.

Background: Recessive mutations in the PTEN induced putative kinase1 (PINK1) gene is a known cause of early-onset Parkinson’s disease (EOPD). The clinical phenotype may vary from typical PD symptoms to dystonia or gait disturbances as the presenting symptom.

Method: In this retrospective study, the patients with PD carrying biallelic PINK1 variants were identified and selected from our database of patients with PD who had undergone exome sequencing. Detailed demographic, clinical data and genetic details of these selected patients were extracted through a chart review.

Results: Five cases (4 females and 1 male) with median age at onset 45 years (Range: 28-53 years) and median duration of 4 years (Range: 1-20 years) were recruited. All patients had asymmetrical onset symptoms, tremor in four patients and slowness in 1 patient. Non motor symptoms of psychosis, depression, ICD, anxiety and mood disturbance was seen in one patient only. All patients were on levodopa, with motor fluctuations in 1 patient and dopa-induced dyskinesia in 2 patients. Consanguineous parentage was noted in 3 patients but none had a positive family history. On examination, none had cognitive impairment and 2 had hypometric saccades. Tremor (isolated rest tremor in 2, rest and postural tremor in 2, isolated postural in 1), bradykinesia and rigidity were noted in all, whereas focal dystonia was noted in 3 patients (hand dystonia in 1, foot dystonia in 2). Pyramidal, sensory and cerebellar examinations were normal. The median UPDRS-III OFF score was 34.5 (Range: 24-53), ON score was 11.5 (Range: 2-16) with improvement of 72% (Range: 54-94). MRI brain was normal in all while FDOPA-PET performed in 1 patient was abnormal. Exome sequencing revealed bi-allelic pathogenic/likely pathogenic variants in all (homozygous-4 patients; compound heterozygous-1 patient). Total 5 unique variants were identified of which 4 were novel (p.Ala291ProfsTer28; p.Asn367del; p.Trp403Ter; exon-5 deletion).

Conclusion: PRK-PINK1 commonly presents as a early-onset PD with tremor predominant phenotype. Non-motor symptoms are infrequent. They have good levodopa responsiveness with early motor fluctuation and dyskinesia. We describe 4 novel pathogenic/likely pathogenic variants in PINK1 associated with the disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinico-genetic-profile-of-five-patients-with-park-pink1-a-case-series-from-india/