Objective: To determine the genetic background of hereditary atypical parkinsonism in an isolated region of the Czech Republic.

Background: A higher prevalence of parkinsonism was recently identified in Southeastern Moravia (Czech Republic). Further research confirmed three large pedigrees with familial autosomal-dominant parkinsonism spanning five generations.

Methods: This case report concerns a patient belonging to one of these three pedigrees, in whom motor and oculomotor symptoms were accompanied by frontal-type dementia, who finally developed a clinical phenotype of supranuclear palsy. Molecular genetic examinations were performed due to the family history; a panel of 16 genes (ADH1C, ATP13A3, EIF4G1, FBXO7, GBA+GBAP1, GIGYF2, HTRA2, LRRK2, MAPT, PARK2, PARK7, PINK1, PLA2G6, SNCA, UCHL1, and VPS35) known to be associated with monogenic familial Parkinson’s disease was tested with a massive parallel sequencing method using Ion Torrent technology and confirmed by Sanger sequencing.

Results: No previously described causal mutation was found. After filtering against common variants (MAF < 0.01), two noncoding and one synonymous rare mutation potentially associable with parkinsonism were identified: GIGYF2 – GRB10 Interacting GYF Protein 2, PARK11 (c.*2030G>A, rs115669549); VPS35 gene – vacuolar protein sorting 35, PARK17 (c.102+33G>A, rs192115886); and FBXO7 – F in box only protein 7, PARK15 (c.540A>G, rs41311141). The VPS35 gene mutation was also confirmed in the patient’s cousin and her two daughters.

Conclusions: Mutations in these genes were previously mentioned only in connection with typical late-onset Parkinson’s disease or “parkinsonism-pyramidal syndrome” disease. This case report presents a new phenotype variant of familial atypical parkinsonism, possibly associated with rare mutations in the FBXO7 and VPS35 genes. This work was supported by Ministry of Health of the Czech Republic – grant Nr. 15-32715A.

« Back to 2016 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/hereditary-atypical-parkinsonism-with-novel-mutation-of-the-vps35-and-fbxo7-genes/