A homozygous parkin p.G284R mutation in a Chinese family with autosomal recessive juvenile parkinsonism.

Autosomal recessive juvenile parkinsonism (AR-JP) is a distinct clinical and neuropathologic entity characterized by early onset parkinsonism and localized neuronal degeneration in the substantia nigra without Lewy bodies. The purpose of this study is to identify the genetic defect in a Chinese pedigree with familial AR-JP and to explore genotype-phenotype correlation. A three-generation Chinese Han pedigree with familial AR-JP was recruited in this study, and the patients in the pedigree presented with typical but heterogeneous clinical features of AR-JP and with different ages of disease onset. Exome sequencing and Sanger sequencing were conducted in the index case diagnosed as juvenile parkinsonism and a homozygous variant, c.850G>C (p.G284R), in the parkin gene was identified. The homozygous variant co-segregated with the disease in the family and was absent in 800 controls. The homozygous variant, c.850G>C (p.G284R), in the parkin gene is possibly responsible for AR-JP in this pedigree. Heterozygous c.850G>C mutation carriers were free of any neurological symptoms, consistent with a loss-of-function mechanism of the parkin mutations. These findings may provide new insights into the cause and diagnosis of AR-JP and have implications for genetic counseling.