Clinical and molecular characterisation of a Parkinson family with a novel PINK1 mutation

Homozygous mutations in the PINK1 gene have been shown to cause early-onset parkinsonism. Here, we describe a novel homozygous mutation (Q126P), identified in two affected German sisters with a clinical phenotype typical for PINK1 -associated parkinsonism.We analysed lactate, pyruvate, carnitine and acylcarnitine blood levels, lactate levels under exercise and in the cerebrospinal fluid, activity of respiratory chain complexes I–IV in muscle biopsies and proteasomal activity in immortalized lymphoblasts, but found no evidence for mitochondrial or proteasomal dysfunction. MR spectroscopy revealed raised myoinositol levels in the basal ganglia of both patients, reflecting possible astroglial proliferation.