We studied the expression of
C9orf72
gene in pathologies associated with hexanucleotide repeats expansion in this gene: frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The ...study included 7 patients with hexanucleotide repeats expansion in the
C9orf72
gene and 9 patients of the control group. The expression of
C9orf72
mRNA was evaluated in blood leukocytes by real-time PCR. Methylation of CpG-sites in
C9orf72
promotor region was evaluated by DNA sequencing after bisulfite conversion. A 2-fold decrease in the
C9orf72
gene expression was found in patients with hexanucleotide repeats expansion in comparison with controls, though the difference did not reach statistical significance due to small sample size. The highest expression was shown for ALS in comparison with FTD and FTD-ALS phenotype. A trend to inverse correlation between
C9orf72
mRNA level and promoter methylation of this gene as well as between mRNA level and age of disease onset was demonstrated.
During a 2-year period in 2005–2007, we conducted surveillance of group A rotaviruses and other enteric agents among patients hospitalized with acute gastroenteritis in 8 different cities of the ...Russian Federation. Fecal specimens were gathered from 3208 children (including 2848 children aged <5 years) and 1354 adults who were admitted to hospitals in Moscow, St. Petersburg, Chelyabinsk, Nizhnii Novgorod, Tyumen, Khabarovsk, Makhachkala, and Yakutsk. Polymerase chain reaction was performed to detect rotaviruses of groups A and C, noroviruses of genogroups I and II, astrovirus, sapovirus, and enteric adenoviruses (group F). Group A rotavirus was the most common viral pathogen detected among children aged <5 years (43.6%), followed by norovirus (12.5%), whereas norovirus was the pathogen most commonly detected in adults (11.9%). P and G genotypes were determined for 515 rotavirus specimens, and the most prevalent genotypes were G1P8 (44.9%), G4P8 (40.0%), G2P4 (8.5%), and G3P8 (6.6%). This study is the first multicenter study of rotaviruses in the Russian Federation and documents the important burden of disease caused by this pathogen, which soon may be preventable by vaccination
Parkinson’s disease (PD) is one of the most common movement disorders. It
is primarily diagnosed clinically. A correct diagnosis of PD in its early
stages is important for the development of a ...pathogenic treatment, which
necessitates a search for potential biomarkers of the disease. We evaluated the
diagnostic value of several microRNAs and their relationship with the clinical
characteristics of PD. The study included 70 PD patients and 40 healthy
volunteers. We analyzed the expression of 15 microRNAs in blood leukocytes,
which were selected based on literature data and modern concepts of molecular
PD pathogenesis. All patients were evaluated using the Hoehn and Yahr scale,
UPDRS, NMSQ, and PDQ-39. The data analysis revealed a statistically significant
increase in the expression of miR-7-5p, miR-29c-3p, and miR-185-5p and a
statistically significant decrease in the expression of miR-29a-3p and
miR-30c-1-5p in leukocytes in PD. However, the altered microRNA profile was
shown to have a moderate diagnostic value for PD diagnosis. MicroRNA expression
changes were associated with the motor and non-motor phenotypic features of PD
and administration of anti-Parkinson’s drugs. Also, a relationship
between some of the microRNAs studied and the duration and severity of PD was
found, which may potentially be used to monitor disease progression.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the HTT gene. HD patient-specific induced pluripotent stem cells (iPSCs) represent an ...excellent model for the disease study. We generated iPSC line from blood mononuclear cells of HD patient with 38 CAG repeats in the HTT exon 1 using integration free episomal plasmids expressing Yamanaka factors. The iPSC line retained the disease causing mutation and expressed pluripotency markers. It also displayed a normal karyotype and the ability to differentiate into derivatives of three germ layers.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by mutation in the HTT gene encoding HTT protein. The mutant protein leads to the neuronal death through ...dysregulation of multiple cellular processes. HD human induced pluripotent stem cells (iPSCs) represent a useful and valid model for the disease study. iPSC line from HD patient with 47 CAG repeats in HTT was generated from blood mononuclear cells by non-integrating episomal vectors. The iPSC line retained the mutation, expressed pluripotency markers, had a normal karyotype and displayed in vitro differentiation to the three germ layers.
Resource table.Unlabelled TableUnique stem cell lines identifierICGi007-AAlternative name(s) of stem cell line47Q-3LfInstitutionFederal Research Center Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, RussiaContact information of distributorElena V. Grigor'evaevlena@bionet.nsc.ruType of cell linesiPSCOriginHumanAdditional origin infoAge: 27Sex: FEthnicity: CaucasianCell SourcePeripheral blood mononuclear cellsClonalityClonalMethod of reprogrammingTransgene free episomal plasmid vectorsGenetic ModificationYESType of ModificationHereditaryAssociated diseaseHuntington's diseaseGene/locusHTT/4p16.3Method of modificationN/AName of transgene or resistanceN/AInducible/constitutive systemN/ADate archived/stock dateDecember 2017Cell line repository/bankhttps://hpscreg.eu/cell-line/ICGi007-AEthical approvalThe generation of iPSC line from cells donated by patient with informed consent was reviewed and approved by “Center of New Medical Technology in Akademgorodok” (protocol No. 21)
Insoluble protein inclusions accumulate in somatic cells in amyotrophic lateral sclerosis. The most common gene mutations associated with this pathology are
SOD1
and
C9orf72
. Protein aggregates can ...be removed from cells by autophagy. We studied the relationship between the presence of genetic abnormalities in the
SOD1
and
C9orf72
genes and changes in autophagy in lymphomonocytes in amyotrophic lateral sclerosis. The study included 85 patients with amyotrophic lateral sclerosis and 15 healthy volunteers. Genetic analysis for the presence of mutations in the
SOD1
and
C9orf72
genes and detection of autophagy marker LC3 in lymphomonocytes were performed. In amyotrophic lateral sclerosis, autophagy activation in lymphomonocytes was found. We also obtained evidence that protein product of the mutant
C9orf72
gene can disturb the late stages of autophagy.
Neurodegeneration in Parkinsons disease is characterized by the accumulation of alpha-synuclein, aprotein encoded by theSNCAgene, in neurons. In addition to mutations, many polymorphisms have been ...identified in this gene, and one of theseis a dinucleotide microsatellite:SNCA-Rep1.The mechanisms by which specific configurations ofSNCA-Rep1 may contribute to the development of this disease have yet to be clarified. Inour study, a relationship between longSNCA-Rep1 alleles and Parkinsons was confirmed in the Russian population. Long allelic variants ofSNCA-Rep1 were shown to be associated with the hypomethylation of the CpG-sites in intron 1 of theSNCAgene. Long variants ofSNCA-Rep1 are supposed to exert their effect through the hypomethylation of atranscriptionally significant region of this gene. Hypomethylation is usually associated with increased expression, which, in turn, contributes to alpha-synuclein accumulation in neuronal cytoplasm, with the latter being the main molecular marker of Parkinsons disease. Further studies are needed to establish a relationship between our finding andSNCAgene expression.
Objectives.
To study the methylation profile of the
FXN
gene and its influence on the formation of the clinical presentation of Friedreich’s disease (FD).
Materials and methods.
The promoter area and ...intron 1 of the
FXN
gene up to the GAA expansion (UP-GAA) and after the GAA expansion (DOWN-GAA) regions were studied in 17 patients with FD, with analysis of a total of 45 CpG sites.
Results.
Studies of genetic-epigenetic interactions identified correlations between the extent of methylation of a series of CpG sites in the UP-GAA and DOWN-GAA and the number of GAA repeats in both expanded alleles of the
FXN
gene in patients with FD. We also found a link between methylation and the presence of the extraneural signs of FD: cardiomyopathy was more likely to be present when the CpG site of the promoter region was hypermethylated, while impairments to carbohydrate metabolism were more common in hypomethylation of CpG sites in the DOWN-GAA area.
Conclusions.
The data obtained here provide evidence that epigenetic modifications of the
FXN
gene make a significant contribution to forming the clinical picture of FD.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary CNS disease with autosomal dominant inheritance caused by
NOTCH3
gene mutations. ...Typically, CADASIL manifests with headaches, recurrent strokes, and progressive cognitive decline. Neuroimaging plays an important diagnostic role as it reveals multiple lacunar infarcts in the basal ganglia, brainstem, and cerebellum, as well as focal white matter lesions and diffuse leukoaraiosis-type changes. CADASIL can sometimes have other symptoms and mimic different phenotypes atypical of the disease. We hereby present two genetically confirmed CADASIL cases that manifested with predominantly cerebellar or essential tremor combined with cognitive and affective disturbances. The main principles of diagnosis of this disease characterized by clinical polymorphism are discussed.
PDF
