Objective: To obtain genetic information about the individuals with confirmed parkinsonism in an isolated rural region in south-eastern Moravia, Czech Republic.

Background: An epidemiological study conducted over four years revealed an increased prevalence of neurodegenerative parkinsonism in a small, isolated region of south-eastern Moravia, Czech Republic. Three large pedigrees with a familial occurrence of parkinsonism were found. Two of them originated in one of the region’s villages; these were compiled into one large family tree with an apparent autosomal-dominant inheritance pattern of parkinsonism spanning generations from 1840 to present.

Methods: Detailed genetic research was performed on the families of all probands with confirmed parkinsonism. Molecular genetic analysis was done in all probands to exclude or confirm the presence of PARK mutations associated with late-onset parkinsonism. Ion Torrent NGS data processing and trimming from FASTAQ through BAM to VCF files was done parallely by Ion Reporter and NexGene software. Variants were than filtered using following parameters: AQ>20; Read coverage >20; MAF<0,002; SIFT: 0 – 0,1; PolyPhen: 0,15 -1; Grantham 6-215.

Results: After filtering out, there were found three missense mutations in LRRK2 gene: rs33995883 in 6/1 patient/control (p/c), rs33958906 in 1/1p/c, undescribed p.Ser633Phe in 3/0p/c, one missense mutation in MAPT gene rs63750072 in 6/1p/c and one mutation in HTRA2 rs72470545 in 3/1p/c.

Conclusions: Our findings together with detailed clinical characteristics of patients could contribute to further understanding of PD molecular pathogenesis. Supported by grant AZV 15-32715A (Czech Republic).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lrrk2-mapt-and-htra2-mutations-in-the-pedigree-of-familial-neurodegenerative-parkinsonism-with-cognitive-deterioration-spanning-five-generations-in-a-genetically-isolated-population-of-south-eastern/