How much phenotypic variation can be attributed to <i>parkin</i> genotype?

TLDR

The study compared phenotypes of 146 patients with parkin mutations to 250 mutation‑negative patients to establish genotype‑phenotype correlations in early‑onset parkinsonism. Patients with parkin mutations showed earlier, more symmetrical onset, dystonia at onset, hyperreflexia, slower disease progression, and a greater levodopa response, while the specific mutation type and location further modulated age at onset, motor severity, and symptom asymmetry. Published in Annals of Neurology, 2003.

Abstract

Abstract To establish phenotype–genotype correlations in early‐onset parkinsonism, we have compared the phenotype of a large series of 146 patients with and 250 patients without parkin mutations. Although no single sign distinguished the groups, patients with mutations had significantly earlier and more symmetrical onset, dystonia more often at onset and hyperreflexia, slower progression of the disease, and a tendency toward a greater response to levodopa despite lower doses. After forward stepwise multiple logistic regression analysis, dystonia at onset and brisk reflexes were not longer significantly different but were correlated with age at onset rather than the presence of the parkin mutation. Age at onset in carriers of parkin mutations varied as did the rate of progression of the disease: the younger the age at onset the slower the evolution. The genotype influenced the phenotype: carriers of at least one missense mutation had a higher United Parkinson's Disease Rating Scale motor score than those carrying two truncating mutations. The localization of the mutations was also important because missense mutations in functional domains of parkin resulted in earlier onset. Patients with a single heterozygous mutation had significantly later and more asymmetrical onset and more frequent levodopa‐induced fluctuations and dystonia than patients with two mutations. Ann Neurol 2003