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). CONCLUSION: 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.

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

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Mensikova K, Kanovsky P, Kaiserova M, et al. Prevalence of neurodegenerative parkinsonism in an isolated population in southeastern Moravia, Czech Republic. PubMed

Mensikova K, Kanovsky P, Otruba P, et al. Epidemiological study of neurodegenerative parkinsonism in “Hornacko”, a specific region of the south-eastern Moravia, Czech Republic.

Mensikova K, Godava M, Kanovsky P, et al. Familial, autosomal-dominant neurodegenerative parkinsonism with cognitive deterioration spanning five generations in a genetically isolated population of south-eastern Moravia, Czech Republic. PubMed

Puschmann A. Monogenic Parkinson's disease and parkinsonism: clinical phenotypes and frequencies of known mutations. PubMed

Respondek G, Höglinger GU. The phenotypic spectrum of progressive supranuclear palsy. PubMed

Pastor P, Pastor E, Carnero C, et al. Familial atypical progressive supranuclear palsy associated with homozygosity for the delN296 mutation in the tau gene. PubMed

Poorkaj P, Muma NA, Zhukareva V, et al. An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype. PubMed

Morris HR, Osaki Y, Holton J, et al. Tau exon 10-16 mutation FTDP-17 presenting clinically as sporadic young onset PSP. PubMed

Ros R, Thobois S, Streichelberger N, et al. A new mutation of the tau gene, G303 V, in early-onset familial progressive supranuclear palsy. PubMed

Donker Kaat I, Boon AJ, Azmani A, et al. Familial aggregation of parkinsonism in progressive supranuclear palsy. PubMed

Höglinger GU, Melhem NM, Dickson DW, et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. PubMed PMC

Ogaki K, Li Y, Takanashi M, et al. Analyses of the MAPT, PGRN and C9or72 mutations in Japanese patients with FTLD, PSP and CBS. PubMed

Fujioka S, Aglom A, Murray EM, et al. Similarities between familial and sporadic autopsy-proven progressive supranuclear palsy. PubMed PMC

Fujioka S, Sanchez-Contreas MY, Strongosky AJ, et al. Three sib-pairs of autopsy-confirmed progressive supranuclear palsy. PubMed PMC

Caroppo P, Le Ber I, Clot F, et al. DCTN1 mutation analysis in families with progressive supranuclear palsy-like phenotypes. PubMed PMC

Zimprich A, Benet-Pagés A, Struhal W, et al. A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson's disease. PubMed PMC

Tsika E, Glauser L, Moser R, et al. Parkinson's disease linked mutations in VPS35 induce dopaminergic neurodegeneration. PubMed PMC

Struhal W, Presslauer S, Spielberger S, et al. VPS35 Parkinson's disease phenotype resembles the sporadic disease. PubMed

Deng H, Liang H, Jankovic J. F-box only protein 7 gene in parkinsonian-pyramidal disease. PubMed

Shoajee S, Sina F, Banihosseini SS, et al. Genome-wide linkage analysis of a parkinsonian-pyramidal syndrome pedigree by 500K SNP Arrays. PubMed PMC

Zhao T, De Graaff E, Breedveld GJ, et al. Loss of nuclear activity of the FBXO7 Protein in patients with parkinsonian-pyramidal syndrome (PARK15). PubMed PMC

Yalcin-Cakmakli G, Olgiati S, Quadri M, et al. A new Turkish family with homozygous FBXO7 truncating mutation and juvenile atypical parkinsonism. PubMed

Di Fonzo A, Dekker MC, Montagna P, et al. FBX07 mutations cause autosomal-recessive, early-onset parkinsonian-pyramidal syndrome. PubMed

Paisan-Ruiz C, Guevara R, Federoff M, et al. Early-onset L-dopa responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations. PubMed PMC

New endemic familial parkinsonism in south Moravia, Czech Republic and its genetical background