- MeSH
- akutní nemoc terapie MeSH
- anamnéza MeSH
- časná diagnóza MeSH
- kojenec MeSH
- lidé MeSH
- management nemoci MeSH
- novorozenec MeSH
- opožděná diagnóza škodlivé účinky MeSH
- terapie náhlých příhod metody MeSH
- vrozené poruchy metabolismu diagnóza terapie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
BACKGROUND: Participation of protein polymorphism is often considered in the pathogenesis of various diseases. Aberrant protein glycosylation has been recognized to play major roles in human disorders, including neurodegenerative diseases. OBJECTIVE: The aim of the study was to examine possible involvement of protein genetic variants and degree of glycosylation of some serum glycoproteins in the manifestation of neurodegenerative disorders in a Czech population sample. METHODS: Apolipoprotein (Apo) E and three main serum markers of glycosylation defects (transferrin, Tf, alpha1-antitrypsin, aAT and ApoCIII) in patients with Alzheimer's dementia (AD), Parkinson's disease (PD) and vascular dementia (n=62, 139 and 44, respectively) were analyzed by isoelectric focusing. Children with serious neurological symptoms (n=55) and three age-matched control groups (n=45, 45 and 42) were examined for comparison. RESULTS: Of the supposedly pathognomonic protein variants Tf C2, aAT ZM and ApoE e4 only the latter was detected with higher frequency in AD patients; significant synergy of the C2/e4 allelic combination was not confirmed. The most prominent finding among PD adults was an increased appearance of Tf C2 allele and significant mean hypoglycosylation of ApoCIII, besides a C2/e4 positive correlation in PD seniors. Laboratory signs of Tf hypoglycosylation and a pattern of Tf/ApoCIII hyperglycosylation have been occasionally found.
- MeSH
- alely MeSH
- alfa-1-antitrypsin krev genetika MeSH
- Alzheimerova nemoc krev genetika MeSH
- apolipoprotein C-III krev genetika MeSH
- apolipoproteiny E krev genetika MeSH
- dítě MeSH
- dospělí MeSH
- frekvence genu MeSH
- glykoproteiny krev genetika MeSH
- glykosylace MeSH
- isoelektrická fokusace MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurodegenerativní nemoci krev epidemiologie genetika MeSH
- Parkinsonova nemoc krev genetika MeSH
- senioři MeSH
- sexuální faktory MeSH
- stárnutí fyziologie MeSH
- transferin genetika metabolismus MeSH
- vaskulární demence krev genetika MeSH
- věkové faktory MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Congenital disorders of glycosylation are a rapidly growing group of inherited (neuro)metabolic disorders characterized by defects in glycosylation of proteins and lipids. This study discusses an analytical problem in the differentiation between hypoglycosylation and transferrin (Tf) protein variants. Analysis of serum Tf by isoelectric focusing is used as a common method suitable for screening 19 out of a total of 22 types of glycosylation defects identified so far. In three members of a family, several indicators showed evidence of a Tf protein variant, however, routine neuraminidase-based demonstration failed to confirm this result. On the assumption that we should be able to exclude Tf protein variants at the screening-level of the diagnostic algorithm, our concern is a possible cause of our failure to confirm some of the Tf D variants (in contrast to the other C, B and D allelic combinations that are commonly well identified). Several explanations are discussed. (c) 2009 Wiley-Liss, Inc.
- MeSH
- dítě MeSH
- dospělí MeSH
- genetické testování MeSH
- glykosylace MeSH
- isoelektrická fokusace MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- protein - isoformy genetika chemie metabolismus MeSH
- transferin genetika chemie metabolismus MeSH
- vrozené poruchy metabolismu sacharidů diagnóza genetika metabolismus MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
BACKGROUND: Genetic polymorphism of serum transferrin (Tf) was studied in order to differentiate between protein genetic variants and congenital disorders of glycosylation (CDG), further focusing on unusual findings. METHODS: Screening of Tf hypoglycosylation was carried out by isoelectric focusing with direct immunofixation and Coomassie blue staining in 100 healthy controls and a group of 1247 patients with various symptoms and diagnoses. RESULTS: Of the seven different genotypes detected, a significantly higher (p = 0.004) frequency of Tf C1C2 was found among 92 patients with cystic fibrosis; only the most severe DF508 mutation (in either homozygous or heterozygous form) was regularly present in the carriers of this Tf genotype, in contrast to those with the Tf C1C1 variant. CONCLUSIONS: Association of Tf C2 allele with various malfunctions has been noticed before, but is so far unresolved. This is the a report on increased frequency of Tf C1C2 genotype found in cystic fibrosis. Analysis of larger samples and independent confirmation of our results are needed.
- MeSH
- cystická fibróza genetika MeSH
- dítě MeSH
- dospělí MeSH
- financování organizované MeSH
- frekvence genu MeSH
- genetická variace MeSH
- genotyp MeSH
- glykosylace MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mutace MeSH
- polymorfismus genetický MeSH
- předškolní dítě MeSH
- transferin genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
Inflammation is a protective immune response to infection, trauma, or injury; however, only a subset of patients develops inflammation, suggesting other contributing factors involved, such as the environment and genes. Inflammationassociated genes involving those with pro- and anti-inflammatory effect should be properly balanced and regulated; the protein products of these genes ultimately determine the outcome of inflammation. Apart from gene mutations, gene polymorphisms related to some inflammatory markers also appear to correlate with the incidence and/or outcome of serious inflammatory events. Some genes recently recognized to be associated with inflammation are briefly reviewed. Modern genomic approaches, such as DNA micro-arrays and serial analysis of gene expression, allow for determining the extremely complex profile of inflammatory genes.
The aim of this paper is to review the diagnostics of congenital disorders of glycosylation (CDG), an ever expanding group of diseases. Development delay, neurological, and other clinical abnormalities as well as various non-specific laboratory changes can lead to the first suspicion of the disease. Still common screening test for most CDG types, including CDG Ia, is isoelectric focusing/polyacrylamide gel electrophoresis (IEF). IEF demonstrates the hypoglycosylation of various glycoproteins, usually serum transferrin. Other methods, such as agarose electrophoresis, capillary electrophoresis, high-performance liquid chromatography, micro-column separation combined with turbidimetry, enzyme-(EIA) and radioimmunoassay (RIA) have also been used for screening. However, these methods do not recognize all CDG defects, so other approaches including analysis of membrane-linked markers and urine oligosaccharides should be taken. Confirmation of diagnosis and detailed CDG subtyping starts with thorough structure analysis of the affected lipid-linked oligosaccharide or protein-(peptide)-linked-glycan using metabolic labeling and various (possibly mass-spectrometry combined) techniques. Decreased enzyme activity in peripheral leukocytes/cultured fibroblasts or analysis of affected transporters and other functional proteins combined with identification of specific gene mutations confirm the diagnosis. Prenatal diagnosis, based on enzyme assay or mutation analysis, is also available. Peri-/post-mortem investigations of fatal cases are important for genetic counseling. Evaluation of various analytical approaches and proposed algorithms for investigation complete the review.
