Pseudo-heterozygous rearrangement mutation of parkin.

ABSTRACT

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 problem-deletion 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.