Objective: We report a Chilean patient with childhood-onset Parkinson’s disease (PD) carrying a single heterozygous PARK7 (DJ-1) mutation and review its clinical and pathophysiological relevance.

Background: Mutations in PARK genes account for approximately 10% of early-onset PD, with PARK7 responsible for about 1% of autosomal recessive cases. DJ-1 encodes a protein acting as a redox sensor, antioxidant and regulator of mitochondrial homeostasis. Loss of function promotes oxidative stress, neuroinflammation and dopaminergic degeneration. Pathogenic phenotypes are usually associated with homozygous or compound heterozygous mutations, while the significance of single heterozygous variants remains controversial.

Method: The clinical features, disease course, treatment response, complementary studies and multigene panel testing of our patient were analyzed. A review of the indexed literature on DJ-1 mutations and associated phenotypes was also performed.

Results: A 33-year-old man developed left-hand tremor at age 8 with slow progression. He showed rapid sustained response to levodopa without motor fluctuations. Non-motor features included impulse control disorder. Examination revealed no rigidity or bradykinesia and mild hand dyskinesias. Brain MRI, metabolic and autoimmune studies were normal. Genetic testing identified a heterozygous DJ-1 variant c.105dup (p.Ala36Cysfs*12). The patient remains functionally independent.

DJ-1 regulates oxidative stress, mitochondrial dynamics and chaperone-mediated autophagy, activating protective pathways. DJ-1–related PD usually presents in early adulthood with good levodopa response and slow progression. Most reported mutations are homozygous or compound heterozygous, although single heterozygous carriers are occasionally described.

Conclusion: DJ-1 plays a key role in neuronal antioxidant defense and mitochondrial stability. However, the pathogenic significance of single heterozygous PARK7 variants remains uncertain. Possible explanations in our case include partial loss of protein function affecting neuronal redox balance, additional variants in deep intronic or regulatory regions not detected by routine panels, or contribution of other genetic factors. This case highlights the need for cautious interpretation of genetic testing and further research into the genetic architecture of early-onset PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dj-1-park7-heterozygous-mutation-and-early-onset-parkinsons-disease-a-chilean-case-report-and-literature-review/