Journal of clinical virology, ISSN 1386-6532 vol. 34, suppl. 1, December 2005
150 s. : il., tab. ; 28 cm
- MeSH
- Hepatitis B, Chronic epidemiology genetics prevention & control MeSH
- Hepatitis B epidemiology genetics prevention & control MeSH
- Hepatitis B Vaccines MeSH
- Hepatitis B virus MeSH
- Publication type
- Conference Proceedings MeSH
- Collected Work MeSH
- Conspectus
- Virologie
- NML Fields
- virologie
- biologie
- hepatologie
Fenomén trpasličích kmenů S. aureus, tzv. Small Colony Variants (SČV), je spojen s chronickými a rekurentními stafylokokovými infekcemi. Tyto fenotypové varianty se liší od kmenů S. aureus s běžným fenotypem nejčastěji velikostí kolonií, jejich morfologií, pigmentací a dalšími znaky, ale také molekulárně genetickými změnami. Příčinou vzniku SCV fenotypu je často mutace v některém z důležitých metabolických či regulačních genů, která je spojena s auxotrofií. Z klinického hlediska je významná zvýšená schopnost SCV kmenů odolávat antibiotické léčbě, zapříčiněná jednak rezistencí k určitým antibiotikům spojenou s příčinou SCV fenotypu a také se schopností těchto kmenů perzistovat uvnitř hostitelských buněk.
The phenomenon of dwarf colonies of S. aureus, the so-called small colony variants (SCVs), is associated with chronic and recurrent staphylococcal infections. Most frequently, these phenotypic variants differ from normal strains of S. aureus in colony size, morphology, pigmentation and other characteristics as well as molecular genetic changes. SCVs frequently emerge as a result of mutations in metabolically important and regulatory genes. The mutations are a cause of SCVs auxotrophy. From a clinical point of view, an increased ability of SCVs to resist antibiotic therapy and also an ability to persist within eukaryotic host cells are of importance.
- MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Cystic Fibrosis drug therapy microbiology MeSH
- Phenotype MeSH
- Hemin MeSH
- Culture Techniques methods statistics & numerical data trends MeSH
- Humans MeSH
- Molecular Biology MeSH
- Mutation genetics MeSH
- Staphylococcal Infections * diagnosis etiology microbiology MeSH
- Staphylococcus aureus * isolation & purification pathogenicity MeSH
- Vitamin K 3 metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Katatonii původně popsal Kahlbaum jako psychomotorický syndrom, který zahrnuje motorické, afektivní a behaviorální příznaky. Začátkem 20. století byla všeobecně přijata myšlenka, že katatonie je motorickým projevem schizofrenie. Dnes chápeme katatonii jako etiologicky heterogenní syndrom, který se může vyskytnout u řady psychických poruch: organických, afektivních, psychogenně navozených, a též u schizofrenních psychóz. Katatonické příznaky můžeme pozorovat u onemocnění na pomezí psychiatrie a neurologie, jako je například neuroleptický maligní syndrom, serotoninový syndrom, benigní stupor, katatonní excitace a další. Pacienti s těžkým psychotickým onemocněním trpí motorickými projevy katatonie asi v 10 %. Výzkumy naznačují, že k vyvolání katatonního syndromu dochází v důsledku hypoaktivity dopaminergního systému a porušení jeho rovnováhy se systémem kyseliny gama ? aminomáselné. Za rizikový faktor se považuje preexistující hypodopaminergní stav, který může být důsledkem organického poškození mozku, akutního nebo chronického stresu, podávání antipsychotik nebo náhlého vysazení dopaminergních látek. Mezi základní léčebné strategie patří podávání benzodiazepinů a elektrokonvulzivní léčba. U maligního neuroleptického syndromu pak podávání dantrolenu, snižování hypertermie a péče o celkový stav.
Catatonia was originally described by Kahlbaum as a psychomotor syndrome involving motor, affective, and behavioral symptoms. At the beginning of the twentieth century it was generally accepted that catatonia is a motoric manifestation of schizophrenia. Today we see catatonia as an etiologically heterogeneous syndrome that may occur with many psychiatric disorders: organic, affective, psychological, and with schizophrenic psychosis. Catatonic symptoms may occur with disorders at borderline between psychiatry and neurology such as neuroleptic malignant syndrome, toxic serotonine syndrome, benign stupor, catatonic excitement and others. About 10 % of patients with severe acute psychiatric illness exhibit motor signs of catatonia. Research implies that catatonia is a consequence of the hypoactivity of the dopaminergic system and its imbalance with the GABA system. Preexisting hypodopaminergic state has been proposed as a risk factor for catatonia. Such state may be a consequence of organic disorder, acute or chronic stress, antipsychotic treatment, or abrupt discontinuation of antipsychotics. Administration of benzodiazepines or electroconvulsive therapy are the primary treatment strategies.
- MeSH
- Benzodiazepines administration & dosage adverse effects therapeutic use MeSH
- Bipolar Disorder diagnosis etiology therapy MeSH
- Brain Damage, Chronic diagnosis etiology MeSH
- Electroconvulsive Therapy methods utilization MeSH
- Drug Therapy methods utilization MeSH
- Catatonia diagnosis etiology drug therapy MeSH
- Humans MeSH
- Neuroleptic Malignant Syndrome diagnosis etiology therapy MeSH
- Schizophrenia, Catatonic diagnosis etiology MeSH
- Serotonin Syndrome diagnosis etiology therapy MeSH
- Transcranial Magnetic Stimulation methods utilization MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.
CONTEXT: While rare variants of the hepatocyte nuclear factor-1 alpha (HNF1A) gene can cause maturity-onset diabetes of the young (HNF1A-MODY), other variants can be risk factors for the development of type 2 diabetes. As has been suggested by the American College of Medical Genetics (ACMG) guidelines for variant interpretation, functional studies provide strong evidence to classify a variant as pathogenic. OBJECTIVE: We hypothesized that a functional evaluation can improve the interpretation of the HNF1A variants in our Czech MODY Registry. DESIGN, SETTINGS, AND PARTICIPANTS: We studied 17 HNF1A variants that were identified in 48 individuals (33 female/15 male) from 20 Czech families with diabetes, using bioinformatics in silico tools and functional protein analyses (transactivation, protein expression, DNA binding, and nuclear localization). RESULTS: Of the 17 variants, 12 variants (p.Lys120Glu, p.Gln130Glu, p.Arg131Pro, p.Leu139Pro, p.Met154Ile, p.Gln170Ter, p.Glu187SerfsTer40, p.Phe215SerfsTer18, p.Gly253Arg, p.Leu383ArgfsTer3, p.Gly437Val, and p.Thr563HisfsTer85) exhibited significantly reduced transcriptional activity or DNA binding (< 40%) and were classified as (likely) pathogenic, 2/17 variants were (likely) benign and 3/17 remained of uncertain significance. Functional analyses allowed for the reclassification of 10/17 variants (59%). Diabetes treatment was improved in 20/29 (69%) carriers of (likely) pathogenic HNF1A variants. CONCLUSION: Functional evaluation of the HNF1A variants is necessary to better predict the pathogenic effects and to improve the diagnostic interpretation and treatment, particularly in cases where the cosegregation or family history data are not available or where the phenotype is more diverse and overlaps with other types of diabetes.
- MeSH
- Biomarkers analysis MeSH
- Diabetes Mellitus, Type 1 genetics metabolism pathology MeSH
- Diabetes Mellitus, Type 2 genetics metabolism pathology MeSH
- Adult MeSH
- Phenotype MeSH
- Hepatocyte Nuclear Factor 1-alpha genetics MeSH
- Humans MeSH
- Mutation * MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
V klinické praxi lze využít jako výstup molekulárně genetického testování pouze prokazatelně patogenní - onemocnění způsobující - mutace. Podhodnocení množství celkově zjištěných patogenních mutací nalezených v rámci mutačního screeningu genů BRCA1 a BRCA2 může být způsobeno existencí obtížně interpretovatelných sekvenčních variant. Ze skupiny 25 sledovaných variant neznámého významu nalezených v rámci screeningu u probandů z vysoce rizikových rodin s dědičným výskytem nádoru prsu a/nebo ovaria bylo po následných analýzách určeno šest patogenních splice site mutací a čtyři polymorfní varianty bez vlivu na nádorovou predispozici. Odlišení patogenních mutací od neškodných polymorfních variant má velký praktický význam pro genetické poradenství. Další příčinou podhodnocení záchytu mutace u vysoce rizikových rodin může být přítomnost velkých intragenových přeskupení nedetekovaných screeningovými testy vycházejícími z PCR reakce. Proto byla u 152 nepříbuzných pacientek diagnostikovaných s dědičnou formou nádoru prsu a/nebo ovaria, které byly negativní po kompletním screeningu kódujících sekvencí BRCA1 a BRCA2 genů, provedena MLPA analýza. Bylo identifikováno 6 různých typů rozsáhlých intragenových delecí v BRCA1 genu celkem u 9 vysoce rizikových rodin. Pomocí MLPA se celkové množství nalezených BRCA1 mutací zvýšilo o dalších téměř 8%.
In clinical practice only true pathogenic - disease causing - mutations can be used as an output of molecular genetic testing. Underestimating of total number of pathogenic mutations detected during BRCA1 and BRCA2 genes mutation screening might be due to existence of sequence variants of unknown significance. The group of 25 unknown variants found in probands from high-risk families with hereditary breast and/or ovarian cancer syndrome was examined. After consequent analysis six pathogenic splice site mutations and four polymorphic variants without an effect on cancer predisposition were determined. Differentiating of pathogenic mutations from common benign polymorphisms is very important for genetic counseling. The presence of large intragenic rearrangements commonly overlooked by PCR-based screening techniques is supposed to be another reason for lower prevalence of pathogenic mutations in high-risk families. MLPA analysis was performed in 152 unrelated patients with hereditary breast and/or ovarian cancer syndrome which were negative after complete screening of coding regions of BRCA1/2 genes. Six different large intragenic deletions in BRCA1 gene were identified in nine of high-risk families. Using MLPA the total number of detected BRCA1 mutations were increased about 8%.
- MeSH
- DNA, C-Form genetics MeSH
- Financing, Organized MeSH
- Genetic Predisposition to Disease genetics prevention & control MeSH
- Genetic Techniques utilization MeSH
- Gene Rearrangement genetics MeSH
- Genes, BRCA1 MeSH
- Genes, BRCA2 MeSH
- Nested Genes genetics MeSH
- Medical Oncology methods trends MeSH
- Humans MeSH
- Breast Neoplasms etiology genetics MeSH
- Ovarian Neoplasms etiology genetics MeSH
- Sequence Analysis, DNA methods utilization MeSH
- RNA Splicing genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Tables MeSH
