Avbersek, A; (2008) Identification of genomic rearrangements in Parkinson's disease genes by multiplex ligation dependent probe amplification. Doctoral thesis , UCL (University College London).

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Abstract

Parkinson's disease (PD) is a neurodegenerative disorder, characterised clinically by tremor, rigidity, bradykinesia, and postural instability. To date, 13 genetic loci have been directly associated with disease. Pathogenic mutations in PD genes associated include single nucleotide changes, small deletions and insertions, as well as large genomic rearrangements. The aim of this study was to screen all familial PD samples held within the Institute of Neurology for genomic rearrangements in SNCA, Parkin, LRRK2, PINK1 and DJ- 1 using the MLPA technique. The DNA samples from 83 patients with familial PD were included, as well as 39 additional DNA samples extracted from the brains of pathologically confirmed PD patients. MLPA analysis was performed using the P051 and P052 probe mixes. We detected heterozygous genomic rearrangements in 9 familial PD patients. These consisted of a rare SNCA duplication, multiple Parkin rearrangements such as exon 2 duplication, exon 8 deletion (2 patients), exon 3 deletion and exons 3 and 4 deletion, PINK1 exon 8 deletion (2 patients) and DJ-1 exons 1 and 3 duplication. For the patients with SNCA and DJ-1 genomic rearrangements, we also described clinical findings. The rare SNCA duplication was confirmed by a genome-wide single nucleotide polymorphysm assay and as a direct result of this project, the family have been contacted and offered genetic counselling.

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