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Familial atypical parkinsonism with rare variant in VPS35 and FBXO7 genes

View Article: PubMed Central - PubMed

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).

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.

No MeSH data available.


Related in: MedlinePlus

Part of the pedigree in which the familiar atypical parkinsonism has been identified (see Ref. [3]). The patient is indicated by the arrow.
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Figure 1: Part of the pedigree in which the familiar atypical parkinsonism has been identified (see Ref. [3]). The patient is indicated by the arrow.

Mentions: A recent epidemiological study performed in southeastern Moravia uncovered a surprisingly high prevalence of parkinsonism compared to other European countries, with an overall 2.8% prevalence in the population over 50 years of age. Subsequently, 3 large pedigrees with an autosomal-dominant (AD) trait with incomplete penetration were identified, all originating in 1 of the local villages.[1–3] Our patient belongs to 1 of these pedigrees (Fig. 1).


Familial atypical parkinsonism with rare variant in VPS35 and FBXO7 genes
Part of the pedigree in which the familiar atypical parkinsonism has been identified (see Ref. [3]). The patient is indicated by the arrow.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120934&req=5

Figure 1: Part of the pedigree in which the familiar atypical parkinsonism has been identified (see Ref. [3]). The patient is indicated by the arrow.
Mentions: A recent epidemiological study performed in southeastern Moravia uncovered a surprisingly high prevalence of parkinsonism compared to other European countries, with an overall 2.8% prevalence in the population over 50 years of age. Subsequently, 3 large pedigrees with an autosomal-dominant (AD) trait with incomplete penetration were identified, all originating in 1 of the local villages.[1–3] Our patient belongs to 1 of these pedigrees (Fig. 1).

View Article: PubMed Central - PubMed

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).

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.

No MeSH data available.


Related in: MedlinePlus