Pseudo-heterozygous rearrangement mutation of parkin

Background: Mutations in parkin are the most frequent cause of autosomal recessive parkinsonism. Quantitative PCR is used to detect parkin rearrangements. However, the method has an inherent problemdeletion and duplication in the same allelic exon could be determined as normal. To present this misidentification, we report a family with compound heterozygous rearrangements in parkin. Methods: A patient with early-onset parkinsonism and the parents were investigated by quantitative PCR, haplotype analysis, reverse-transcription PCR, and direct sequencing. Results: A single heterozygous duplication (duplication of exons 6-7) was identified in the patient by quantitative PCR. Detailed analysis of the family revealed the patient carried compound heterozygous of combined deletion (deletion of exons 3-5) and duplication (duplication of exons 3-7). Conclusions: For correct determination of rearrangement mutation, mutation analysis of the patient as well as other family members and/ or break-point analysis of genomic DNA and at the transcript level should be conducted. (C) 2012 Movement Disorder Society