Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Genetics
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
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.
To cite this abstract in AMA style:
K. Mensikova, T. Bartonikova, L. Mikulicova, R. Vodicka, R. Vrtel, M. Godava, I. Dolinova, M. Vastik, M. Kaiserova, P. Otruba, P. Kanovsky. Hereditary atypical parkinsonism with novel mutation of the VPS35 and FBXO7 genes [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/hereditary-atypical-parkinsonism-with-novel-mutation-of-the-vps35-and-fbxo7-genes/. Accessed May 15, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/hereditary-atypical-parkinsonism-with-novel-mutation-of-the-vps35-and-fbxo7-genes/