Objective: To evaluate the interest of the MLPA (Multiplex Ligation-dependent Probe Amplification) commercially available kit in the genetic testing in Parkinson’s disease (PD).

Background: PD is a multifactorial disorder and genetics play an important role in its pathogenesis. Since the last decades, point mutations and genomic rearrangements were detected in several genes (mainly SNCA, LRRK2, PRKN, PINK1 and DJ1). MLPA is a cheap, simple and rapid method that allows to detect exon dosage alterations and point mutations in selected genes.

Method: Between 2007 and 2019, 691 DNA samples were addressed to the Lille University Hospital genetic laboratory in order to identify mutations in PD patients. Among them, 544 samples were unique and belonged to independent families. The majority of samples (72%) came from the Movement Disorders Unit of the Lille University Hospital. All the patients gave their written consent to the genetic analyses. The genetic testing was performed using the SALSA MLPA kits P051 and P052 (MRC Holland) according to the manufacturer’s instructions. Rearrangements and point mutations detected were verified by conventional PCR.

Results: Genomic rearrangements such as exon deletions or multiplications were found in the PRKN gene for 24 PD patients and in the SNCA gene for 4 patients. The G2019S LRRK2 point mutation was found in 20 other PD patients. Overall, the MLPA kit allowed to identify genetic mutations in 8.8% of the cohort. All these patients had either young-onset of PD (age at onset ≤ 45 years) either a family history of PD.

Conclusion: With this high level of positive result, we confirm the interest in using this rapid and cheap method in order to identify genetic mutations in PD before next-generation sequencing methods like whole exome sequencing. Moreover, these results highlight the importance of screening genetic copy number variants in PRKN and SNCA that are not infrequent and can be missed with sequencing methods.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/interest-of-multiplex-ligation-dependent-probe-amplification-assay-to-identify-pathogenic-mutations-in-parkinsons-disease-patients/