Objective: To report the clinico-radiological phenotype and progression of a female proband and her parents with mutations in the PRKN gene.

Background: Bi-allelic PRKN mutations are the most frequent cause of early-onset Parkinson’s disease and are inherited in an autosomal recessive pattern with high penetrance.1 The typical phenotype is that of levodopa-responsive motor parkinsonism, with a predilection for dystonia, dyskinesias and motor fluctuations. Parkin, the protein product of PRKN, is involved in ubiquitination and degradation of proteins, and mitochondrial quality control via mitophagy. Deep clinical phenotyping may improve understanding of the natural history and genotype-phenotype correlations in PRKN-related Parkinson’s disease.

Method: We present a clinico-radiological update on a family with mutations in PRKN, whose unique phenotypic variability was first reported in 2012 (1).

Results: The proband is a 54-year-old female who first developed signs of parkinsonism at the age of 19. Genetic testing revealed compound heterozygous mutations (c.8_171del / c.535_871del, p.V3EfsX3 / p.G179LfsX7) in PRKN. Dopamine transporter imaging at age 31 showed moderately reduced dopamine uptake in the putamen bilaterally, which had progressed on repeat imaging at age 54. Presently, she is treated with continuous subcutaneous foslevodopa/foscarbidopa infusion and rasagiline. Her motor symptoms are generally well controlled, with intermittent dyskinesias and dystonias. Significant non-motor symptoms include sleep fragmentation, rapid eye movement (REM) sleep behaviour disorder, and depression. The proband’s 79-year-old mother and 80-year-old father both exhibit non-specific slowness of movement in the context of medical comorbidities. Neither have overt motor or non-motor features of Parkinson’s disease. The father had a single heterozygous PRKN mutation (c.535_871del / p.G179LfsX7), and the mother had homozygous PRKN mutations with complete exon 2 deletion (c.8_171del / p.V3EfsX3). Despite her homozygous status, the mother has yet to develop clinically overt Parkinson’s disease by her eighth decade and demonstrates normal dopamine transporter imaging.

Conclusion: Patients harbouring homozygous or compound heterozygous PRKN mutations may have significant variability in their clinical phenotype and dopamine transporter imaging.

References: 1. Koentjoro B, Park JS, Ha AD, Sue CM. Phenotypic Variability of parkin Mutations in Single Kindred. Movement Disorders. 2012;27(10):1299-1303.

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/clinico-radiological-phenotype-of-a-unique-family-with-mutations-in-prkn-over-three-decades/