title: Familial atypical parkinsonism with rare variant in VPS35 and FBXO7 genes: A case report.
abstract: BACKGROUND
  A higher prevalence of parkinsonism was recently identified in southeastern Moravia (Czech Republic). Further research confirmed 3 large pedigrees with familial autosomal-dominant parkinsonism spanning 5 generations.
  
  
  METHODS
  This case report concerns a patient belonging to one of these 3 pedigrees, in whom motor and oculomotor symptoms were accompanied by frontal-type dementia, who finally developed a clinical phenotype of progressive supranuclear palsy. Molecular genetic examinations were performed due to the positive family history.
  
  
  RESULTS
  No previously described causal mutation was found. After filtering against common variants (minor allele frequency (MAF) < 0.01), 2 noncoding and 1 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-box only protein 7 gene, PARK15 (c.540A > G, rs41311141).
  
  
  CONCLUSIONS
  As to the changes in the FBXO7 and VPS35 genes (despite phylogenetic conservation in primates), probably neither the FBXO7 nor the VPS35 variants will be direct causal mutations. Both described variants, and possibly the influence of their combination, could increase the risk of the disease.
authors.affiliation: Department of Neurology Department of Medical Genetics and Fetal Medicine, Faculty of Medicine and Dentistry, Palacky University, University Hospital, Olomouc Department of Nanomaterials in Natural Sciences, Technical University, Liberec, Czech Republic.
authors.forename: Tereza
authors.initials: T
authors.lastname: Bartonikova
authors.forename: Katerina
authors.initials: K
authors.lastname: Mensikova
authors.forename: Lenka
authors.initials: L
authors.lastname: Mikulicova
authors.forename: Radek
authors.initials: R
authors.lastname: Vodicka
authors.forename: Radek
authors.initials: R
authors.lastname: Vrtel
authors.forename: Marek
authors.initials: M
authors.lastname: Godava
authors.forename: Miroslav
authors.initials: M
authors.lastname: Vastik
authors.forename: Michaela
authors.initials: M
authors.lastname: Kaiserova
authors.forename: Pavel
authors.initials: P
authors.lastname: Otruba
authors.forename: Iva
authors.initials: I
authors.lastname: Dolinova
authors.forename: Martin
authors.initials: M
authors.lastname: Nevrly
authors.forename: Petr
authors.initials: P
authors.lastname: Kanovsky
mesh_terms: D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging; D044783:F-Box Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009154:Mutation; D020734:Parkinsonian Disorders / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: D044783:F-Box Proteins; C489149:FBXO7 protein, human; C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins