Objective: Analysis of positive LRRK2 and GBA gene mutations, demographic characteristics, and family history in 1200 consecutive Ashkenazi patients with PD who had genetic testing for LRRK2 and GBA mutations.

Background: Patients with Parkinson’s disease who are of Ashkenazi Jewish descent may have a LRRK2 and/or GBA gene mutation. Approximately 30-40% of unaffected LRRK2 gene carriers and approximately 8% of GBA gene carriers may develop clinical motor PD during their lifetime. It is unknown if PD diagnosis occurs earlier in life due to the LRRK2 or GBA gene, or if elderly have lower vs. higher risk.

Methods: Genetic testing was conducted at our site through the MJFF PPMI genetic screening program. We reviewed prodromal clinical characteristics of unaffected relatives of PD patients and also of patients already diagnosed with PD who were found to have the LRRK2 and/or GBA gene mutation associated with Ashkenazi PD. We also compared these gene positive to those who were tested but did not have these gene mutations. We also compared PD gene-positive and gene-negative with a family history of PD to those without.

Results: Over 1200 patients underwent genetic testing after clinical counseling for LRRK2, and approximately half of these for GBA gene too. Of 350 unaffected relatives with a PD family history tested, 32 had LRRK2 gene mutation and 150 were also tested for GBA with 10 with a GBA gene mutation. Of 850 patients with PD, approximately 50% of patients reported a known family history of PD. Of patients with a family history, 48 had LRRK2 gene and 18 had GBA gene. Of patients with PD not reporting a family history of PD, 24 had LRRK2 gen and 12 had GBA gene.

Conclusions: Routine gene testing of patients with PD who have Ashkenazi heritage (ie one grandparent) may be of value as these genes seem relatively common in patients reporting a known family history of PD and ven in those unaware of a PD family history, As new therapies enter clinical development, PD patients of Ashkenazi descent will need counseling that LRRK2 and GBA gene mutations are not uncommon, have autosomal dominant inheritance to to their children, and may be amenable to trials of emerging therapies seeking to slow or retard progression of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lrrk2-and-gba-genetic-mutations-are-not-uncommon-in-an-unselected-ashkenazi-elderly-cohort-with-pd/