Novel ATP13A2 (PARK9) homozygous mutation in a family with marked phenotype variability

Mutations in the ATP13A2 (PARK9) and FBXO7 (PARK15) genes are linked to different forms of autosomal recessive juvenile-onset neurodegenerative diseases with overlapping phenotypes, including levodopa-responsive parkinsonism, pyramidal disturbances, cognitive decline, and supranuclear gaze disturbance. However, the associated genotypes and phenotypes are poorly characterized due to the small number of patients described. Here, we report clinical, instrumental, and genetic findings in an Italian family with novel PARK9 and PARK15 mutations. The proband developed a severe progressive phenotype including juvenile-onset parkinsonism, pyramidal disturbances, cognitive decline, and oculomotor abnormalities. On the contrary, his brother only shows mild abnormalities (pyramidal, cognitive, and oculomotor) on the neurological examination at the age of 31 years. These two brothers both carry a novel homozygous PARK9 missense (p.G877R) and a novel heterozygous PARK15 mutation (p.R481C). The PARK9 mutation replaces a crucial residue for the ATPase activity, and is therefore most likely a loss-of-function mutation and disease-causing in homozygous state. The pathogenic significance of the PARK15 single heterozygous mutation remains unclear. In both sibs, DaTSCAN single photon emission computed tomography showed marked nigrostriatal dopaminergic defects, and transcranial magnetic stimulation detected prolonged central motor conduction time. MRI, including T2*-weighted imaging, detected no evidence of brain iron accumulation. This family, the third reported with homozygous PARK9 mutations and the first with mutations in two genes for atypical juvenile parkinsonism, illustrates that PARK9-linked disease might display wide intra-familial clinical variability and milder phenotypes, suggesting the existence of strong, still unknown, modifiers

Parkinsonian phenotype in Machado-Joseph disease (MJD/SCA3): a two-case report

Background: Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder of late onset, which is caused by a CAG repeat expansion in the coding region of the ATXN3 gene. This disease presents clinical heterogeneity, which cannot be completely explained by the size of the repeat tract. MJD presents extrapyramidal motor signs, namely Parkinsonism, more frequently than the other subtypes of autosomal dominant cerebellar ataxias. Although Parkinsonism seems to segregate within MJD families, only a few MJD patients develop parkinsonian features and, therefore, the clinical and genetic aspects of these rare presentations remain poorly investigated. The main goal of this work was to describe two MJD patients displaying the parkinsonian triad (tremor, bradykinesia and rigidity), namely on what concerns genetic variation in Parkinson's disease (PD) associated loci (PARK2, LRRK2, PINK1, DJ-1, SNCA, MAPT, APOE, and mtDNA tRNAGln T4336C). Case presentation: Patient 1 is a 40 year-old female (onset at 30 years of age), initially with a pure parkinsonian phenotype (similar to the phenotype previously reported for her mother). Patient 2 is a 38 year-old male (onset at 33 years of age), presenting an ataxic phenotype with parkinsonian features (not seen either in other affected siblings or in his father). Both patients presented an expanded ATXN3 allele with 72 CAG repeats. No PD mutations were found in the analyzed loci. However, allelic variants previously associated with PD were observed in DJ-1 and APOE genes, for both patients. Conclusions: The present report adds clinical and genetic information on this particular and rare MJD presentation, and raises the hypothesis that DJ-1 and APOE polymorphisms may confer susceptibility to the parkinsonian phenotype in MJD

Audio application as a mean of Chinese students’ e-learning

Presents an audio application for Chinese students taking preliminary mathematics courses taught in Russian and aspiring to get higher education in Russia. The audiovisual materials provided help to develop foreign students’ listening comprehension skills, deepening their knowledge both in the Russian language and mathematics. Audio application can be used without teachers’ guidance

Breakpoint mapping of 13 large parkin deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations

Early-onset Parkinson’s disease (EOPD) has been associated with recessive mutations in parkin (PARK2). About half of the mutations found in parkin are genomic rearrangements, i.e., large deletions or duplications. Although many different rearrangements have been found in parkin before, the exact breakpoints involving these rearrangements are rarely mapped. In the present study, the exact breakpoints of 13 different parkin deletions/duplications, detected in 13 patients out of a total screened sample of 116 EOPD patients using Multiple Ligation Probe Amplification (MLPA) analysis, were mapped using real time quantitative polymerase chain reaction (PCR), long-range PCR and sequence analysis. Deletion/duplication-specific PCR tests were developed as a rapid and low cost tool to confirm MLPA results and to test family members or patients with similar parkin deletions/duplications. Besides several different deletions, an exon 3 deletion, an exon 4 deletion and an exon 7 duplication were found in multiple families. Haplotype analysis in four families showed that a common haplotype of 1.2 Mb could be distinguished for the exon 7 duplication and a common haplotype of 6.3 Mb for the deletion of exon 4. These findings suggest common founder effects for distinct large rearrangements in parkin

Chemical composition of leaf extracts of Stevia rebaudiana Bertoni grown experimentally in Vojvodina

The chemical composition of leaf extracts of Stevia rebaudiana Bertoni, grown for the first time on an experimental field near Zrenjanin, was examined by GC–MS. The tested plant material was harvested in September of 2002. To analyze the chemical composition of the lipophilic components of the plant leaves, essential oils and ethyl acetate extract were isolated. Qualitative analysis of the essential oil obtained by hydrodistillation showed that among the identified 88 compounds, the majority were mono- and sesquiterpenes (50 types identified). By analysing the ethyl acetate extract, the presence of fatty acids (present as free and as esters), n-alkanes, n-alkenes, cyclic alkanes, alcohols, aldehydes, ketones, etc. was ascertained. Sesquiterpenes prevailed among the terpenes (50 types identified). Further constituents identified in ethyl acetate extract included sterols. Nerol, b-cyclocitral, safranal, aromadendrene, a-amorphene and T-muurolol were identified for the first time in this species, with match values over 90 %. Taking into consideration that these terpenes were identified for the first time in this species, it is obvious that Stevia rebaudiana grown in this area possesses certain specific characteristics that can be ascribed to cultivation on a domestic plantation