Objective: To present and discuss a series of 7 patients with early-onset Parkinson’s Disease and heterozygosity for PARK2 mutation.

Background: Parkin mutation in homozygosity or compound heterozygosity is well known as a major cause of autosomal recessive PD. It typically results in early-onset PD (EOPD) with relatively benign progression and good response to dopaminergic therapy. The role of heterozygosity for parkin mutations in the etiology and pathophysiology of PD is currently unknown.

Methods: Clinical characterization of a series of patients with heterozygosity for parkin mutation who were diagnosed with PD before age 50. Mutations in other genes (LRRK2, SNCA, PINK1, DJ1 and GBA) were assayed by direct sequencing and/or multiplex ligation-dependent probe amplification.

Results: Total of 7 patients, with female predominance (n=5, 71.4%). Mean age at onset of symptoms was 46.6 years (±2) and the mean time of disease evolution is 11.7 years (±8). There is a positive family history in only 2 (28.5%) cases. The presentation form was an akinetic-rigid syndrome in 6 (85.7%) patients. Dyskinesia with low doses of levodopa occurred in 6 patients (85.7%), with early dystonic phenomena in 2 cases (28.5%). There is no cognitive decline in 6 (85.7%) patients. The remaining patient has a more severe phenotype with cognitive decline at 14 years of disease evolution. All patients are heterozygous for either parkin gene point mutation (n=6, 85.7%) or exon triplication (n=1, 14.3%). No mutations were identified in the remaining genes studied.

Conclusions: The influence of heterozygosity for parkin mutation in the development of PD remains controversial. We present a series of 7 heterozygous patients with EOPD, aiming to further the discussion on the putative correlation between phenotype and genotype.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-onset-parkinsons-disease-in-seven-patients-with-heterozygosity-for-parkin-mutation/