Dr. Mei Sun

Mei Sun, MD, PhD, of the Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston, and colleagues in the international GenePD Study evaluated the effects of parkin mutations in 183 of 329 families with at least two Parkinson’s disease–affected members. Two criteria were used in the selection process: (1) families with affected siblings sharing two alleles identical by state at the PARK2 locus and (2) families in which one person had onset before age 54.

At least one parkin mutation was found in 23 of 183 patients (12.6%), the investigators reported. Among mutation-positive families, 10 (43%) were compound heterozygotes, three (13%) were homozygotes, and 10 (43%) were heterozygotes.

Patients with parkin mutations developed Parkinson’s disease at an average age of 42.9—a mean 11.7 years earlier than patients with no mutation, said Dr. Sun. Patients with two or more mutations had an onset 13.2 years earlier than patients with a single mutation.

"Parkin mutations are not rare in this selected subset of familial Parkinson’s disease samples. Homozygous and compound heterozygous parkin gene mutations are associated with early-onset Parkinson’s disease (mean onset age, 36)," the investigators said. Though parkin mutations were presumed recessive, the data on the heterozygous individuals suggest that the gene’s effect may be stronger than previously recognized, Dr. Sun noted.