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Abstract Details

The Challenge of Genetic Counselling in Early Onset Parkinsonian Disorders
Movement Disorders
P2 - Poster Session 2 (8:00 AM-9:00 AM)
3-017
The study analyses the genetic background of early-onset Parkinsonism (EOPD) in a Hungary and evaluated the clinical usefulness of genetic investigations and the challenges of the genetic counselling of these cohort.  
The genetic analysis of  is part of the clinical diagnostics.  Increasing number of genes have been implicated in the genetic background of EOPD, which is clinically indistinguishable from idiopathic Parkinson's disease. The identification of patient's genotype could support clinical decision-making process and also track and analyse outcomes in a comprehensive fashion. 
To identify genetic alterations MLPA and Sanger sequencing of the most common PD-associated genes was performed in 142 PD patients. Next-generation sequencing (NGS) of 127 genes which were previously associated to neurodegenerative disorders were carried out in 54 cases. The e?ect of rare variant burden on the age at onset of the disease was analysed with ANOVA test. We examine the possibility of oligogenic e?ect variant burden in individuals as well. 
The genetic analysis identified several heterozygous damaging substitutions or CNVs in PD-associated genes (C19orf12, DNAJC6, DNAJC13, EIF4G1, LRRK2, PRKN, PINK1, PLA2G6, SYNJ1, PRKN, SNCA)
In our cohort 9 previously published genetic risk factors were detected in 3 genes (GBA, LRRK2, PINK1). In 9 cases, 2 or 3 coexisting pathogenic mutations and risk variants were identified.
Rare damaging variants were enriched vs neutral variants, among Hungarian PD patients, which raise the possibility of an oligogenic effect. Heterozygous mutations of multiple recessive genes involved in the same pathway may perturb the molecular process linked to PD pathogenesis. Monogenic cause in EOPD have been revealed rarely, however the involvement of multiple PD-associated genes may facilitate the better understanding of clinically distinct phenocopies. Due to the genetic complexity of the disease, genetic counselling is getting more challenging.

Authors/Disclosures
Maria J. Molnar, MD, PhD (Neurorex BT)
PRESENTER 		Dr. Molnar has nothing to disclose.
Peter Balicza No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file