Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Variant interpretation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,531 records · Page 85Linked to original sources
PubMed1992

Error in radiology: classification and lessons in 182 cases presented at a problem case conference.

The authors review and classify errors in 182 cases that were presented at problem case conferences between August 1986 and October 1990. Errors were classified by means of a system developed 20 years ago and by means of a system developed within the past several years. The authors found that sources of error have changed very little. Errors usually involved failure to consult old radiologic studies or reports, limitations in imaging technique, acquisition of inaccurate or incomplete clinical history, location of a lesion outside the area of interest on an image, lack of knowledge, failure to continue to search for abnormalities after the first abnormality was found, and failure to recognize a normal biologic variant. Errors included 126 perceptual errors (64 false-negative, 15 false-positive, and 47 misclassification errors) and 56 mishaps, including 38 complications and 18 communication errors. In seven cases nonperception errors occurred because established departmental routines were not followed, and in nine cases a new departmental routine was established after a complication occurred. Departmental policy exerts less effect on perception and interpretation errors.

Diagnostic Errors↗
PubMed2005

Reduced DNA repair capacity in laryngeal cancer subjects. A comparison of phenotypic and genotypic results.

The impact of genetic factors on laryngeal cancer risk was studied in relation to DNA repair capacity on the phenotypic and genotypic level. DNA lesions induced by bleomycin or S9-activated benzo[a]pyrene were determined in blood lymphocytes using the alkaline comet assay. Laryngeal cancer subjects (n = 52) were shown to have higher levels of spontaneous and mutagen-induced DNA damage as compared to healthy controls (n = 56). A level of spontaneous DNA damage tended to increase with tumour grading. A percentage of individuals with an efficient DNA repair was higher in controls than in cancer subjects for both used mutagens. The distribution of polymorphic variants of XPD, XRCC1 and XRCC3 DNA repair genes in the group of laryngeal cancer subjects (n = 293), subjects with second primary tumours (n = 84) and in the matched controls (n = 322) was estimated by PCR-based genotyping. Five polymorphisms were studied in 3 DNA repair genes. There were found only 2 XPD alleles significantly overrepresented in laryngeal cancer that could be interpreted as an increase in genetic risk. There were no significant differences in distribution of 'risk' and 'protective' genotypes between single primary and second primary tumours. Altogether, the established phenotypic deficit of DNA repair in laryngeal cancer subjects was only partly confirmed by overrepresentation of 'risk' genotypes of the studied DNA repair genes.

Adult↗
PubMed2000

Avian reovirus infections.

Avian reoviruses are ubiquitous among poultry flocks. Although infection is usually present without disease, reoviruses may occasionally be involved in several disease syndromes of which viral arthritis/tenosynovitis in chickens is the most important, particularly in broiler breeds. While reoviruses have been isolated from turkeys and several other species of birds with various conditions, the presence of the virus has been conclusively linked with disease in relatively few instances. In chickens in particular, avian reoviruses with a wide spectrum of pathogenic capability have been isolated and several antigenic types exist. Diagnosis is dependent on the detection of the virus in clinical samples, although the presence of the virus does not necessarily confirm that this is the cause of the disease, except where reoviruses are detected in affected joints. Serological tests are usually difficult to interpret in view of widespread and frequently harmless reovirus infection. The principal approach to control of viral arthritis/tenosynovitis is by vaccination using attenuated vaccines in young birds, followed by inactivated preparations for breeders intended to protect chicks by maternal antibodies. Many vaccines are based on the S1133 strain isolated in the United States of America, but these may not be effective against antigenic variants.

Animals↗
PubMed2003

[Pulmonary veno-occlusive disease in a patient with scleroderma and the CREST syndrome].

BACKGROUND: Pulmonary veno-occlusive disease is a rare and poorly understood condition that affects the postcapillary pulmonary vasculature, posing diagnostic problems and treatment dilemmas. MATERIALS AND METHODS: We present a patient with veno-occlusive disease and give a short review on the disease. RESULTS: The patient was a 54-year-old female with a history of the CREST variant of scleroderma. Admitted with dyspnoea, she was treated with epoprostenol in addition to oxygen, diuretics and warfarin. Epoprostenol improved her condition initially; her symptoms grew worse during further medical escalation. With an attempt to stop epoprostenol, however, she became even more dyspnoeic and tolerated best an intermediate dose. She died after three months of treatment with signs of progressive right heart failure. INTERPRETATION: Veno-occlusive disease may be difficult to diagnose and treat. Clinical signs of pulmonary hypertension without evidence of left ventricular failure may give rise to suspicion of the disease, and high-resolution CT of the lungs with relatively specific findings can be helpful. The prognosis is poor and lung transplantation is the only form of effective treatment. Vasodilators as a bridge to transplantation must be used with caution because of the risk of intolerance and development of pulmonary oedema.

Antihypertensive Agents↗
PubMedDate not supplied

[The Northern variant of the norm in the thermal picture of the face].

One hundred and ten healthy residents of the cities of Krasnoyarsk and Norilsk were examined using the method of thermal visualization. As a result, a symptomcomplex of the thermal face picture typical of the Northern version of the norm was detected and described. When compared to the controls from Krasnoyarsk, delta T of the target group from Norilsk was on the average 0.07 degrees C lower. The knowledge of the thermal normogram in the Far North can help adequately interpret face thermograms of patients with nasal and paranasal pathologies in different geographical regions.

Adult↗
PubMed1975

[Some characteristics of the state of the sympatho-adrenal system in various hemodynamic variants of hypertension].

In 40 patients with umcomplicated hypertension their general haemodynamics was compared with the excretion of catecholamines and their metabolites. On the initial stage of the disease the hormonal link was found to prevail over the mediator one; the decreasing excretion of bound catecholamines after the administration of Isuprel indicates that a disbalance between the secretion and inactivation of catecholamines develops as early as on this stage of the disease. Later, in resistance hypertension the administration if Isuprel resulted in an increased excretion of free noradrenalin, which is interpreted as a sign of increased reactivity of this link; no such reaction is noted in ejection hypertension. A study of all these links of the sympathoadrenal system is important for the understanding of the pathogenesis of hypertension and for the choice of this therapy.

Adolescent↗
PubMed2000

Modelling the transition of asexual blood stages of Plasmodium falciparum to gametocytes.

In this paper, we investigate the transition of asexual blood stages of P. falciparum to gametocytes. The study is based on daily data, collected from 262 individual courses of parasitaemia. We propose several mathematical models that follow biological reasoning. The models are fitted with maximum likelihood and are compared with each other. The models differ in the assumptions made about the mortality of circulating gametocytes and about the transition rate of the asexual parasites. Gametocyte mortality is modelled as being (i) constant over time, (ii) linearly increasing over time, (iii) linearly increasing over gametocyte age, and (iv) exponentially increasing over gametocyte age, respectively. The transition rate is either kept constant per patient or piecewise constant within intervals that correspond to waves of asexual parasitaemia which are assumed to be caused by different Pf(emp1)-variants. According to likelihood ratio tests, the models with age-dependent mortality rate and wave-dependent transition rates are superior to the models with constant transition rate and/or constant or time-dependent mortality rate. The best fits are reached for models with exponentially increasing (Gompertz-type) mortality. Furthermore, an impact of high asexual parasite densities on the survival of gametocytes, interpreted as a cytokine-mediated effect, is evident in some cases.

Animals↗
PubMed2003

Genetics and clinical practice in rheumatology.

The dramatic advances made recently in human genome research are fueling considerable interest in genetic testing. A specific feature of genetic testing is that the results are final and impact not only the patient, but also the entire family. Those elements should be factored into the risk/benefit ratio evaluation. In France, legislation the differentiates diagnostic tests in symptomatic patients from predictive tests in asymptomatic patients with affected family members. Only multidisciplinary groups with both clinical and genetic expertise can order predictive tests. In all cases the physician must sign a statement that informed consent was obtained from the patient prior to testing. The test must be done in an accredited laboratory and the result communicated by the physician to the patient. Patient confidentiality must be respected, particularly regarding family members. In monogenic diseases, the diagnostic weight of genetic testing is often considerable, although the limitations should be borne in mind. In multifactorial diseases, genetic testing seeks to identify risk factors that are usually associated with a low level of risk. The result should be interpreted in the light of the clinical presentation, family history, and genetic background. The predictive value is closely dependent on the clinical presentation but is generally limited, most notably when family members are affected. Great care should be taken to avoid causing undue anxiety among individuals with positive test results. Diseases that illustrate these aspects include Paget's disease of bone, of which inherited variants caused by a mutation in a single gene on chromosome 5 have been identified recently, and rheumatoid arthritis, which is a multifactorial disease.

Connective Tissue Diseases↗
PubMed2002

Spike-wave discharge and the microstructure of sleep-wake continuum in idiopathic generalised epilepsy.

This review summarises all the evidences about the influence of different vigilance states on the occurrence of spike wave discharge (SWD) in idiopathic generalised epilepsy (IGE) patients. Numerous converging observations showed that full REM-sleep and alert wakefulness exert strong inhibition. A critical zone of vigilance which is a transitional state between waking and non-REM (NREM) sleep, and NREM sleep and REM sleep, has a promoting effect on the absence type spike wave discharge. Spike wave discharges are associated with phasic arousals without awakening and are attached to oscillation son the microstructural level of sleep, perpetuated by cyclic arousal events known as 'cyclic alternating pattern' (CAP), especially within the critical zone, but also along the whole sleep process. More specifically SWD seems to be attached to the 'A-phase' of CAP which is a reactive one and reflects synchronised NREM sleep EEG elements, like K-complexes, spindles and delta groups. The more slow wave elements are found in phase A--like in subtype A1--the more the coincidence with SWD occurs, and the more it is characterised by fast rhythms--as in subtype A2 and A3--the less the association with SWD could be observed. Since subtype A1 is associated with the first sleep cycle and with the descending branches of cycles, it is concluded that SWD appear in those dynamic moments of vigilance level oscillations which were characterised by strong sleep-like answers to arousal influences in high sleep pressure periods of sleep cyclicity. These data harmonize with another line of evidence suggesting that SWD represent the epileptic variant of the complex thalamocortical system function which is the substrate of NREM sleep EEG phenomena. In idiopathic generalised epilepsy there is a growing body of evidence that--as it was assumed by Gloor--spindles transform to SWD pattern. These data explain why those dynamic changes which evoke sleep responses are promoting for the occurrence of SWD. Adapting these data we offer a new interpretation to explain the strong activation effect of sleep deprivation in this kind of epilepsy. We assume that it is mainly due to the forced vigilance level oscillations, especially in morning, when elevated sleep pressure and circadian wake promoting forces, representing opposite tendencies, increase the amount of oscillations.

Epilepsy, Generalized↗
PubMed1994

[Kleptomania before and after spontaneous subarachnoid hemorrhage--a neuropsychodynamic case report].

Kleptomania is not supposed to be a nosologic entity, but represents a psychopathological symptom of variant neurological and psychiatric diseases. A 47-year-old woman had shown a kleptomanic impulse disorder on the basis of a phobic personality organisation, until she suffered a spontaneous subarachnoidal haemorrhage with a consecutive basal forebrain lesion five years ago. After this event the kleptomanic symptom worsened dramatically. This case suggests an integrated "neuropsychodynamic" approach to clinical findings, which are commonly to be interpreted neuropsychologically and psychodynamically. We discuss the many mutual overlappings of neurobiologically determined and biographically understandable psychic phenomena.

Disruptive, Impulse Control, and Conduct Disorders↗
PubMed1999

Thermal stability of hydrophobic heme pocket variants of oxidized cytochrome c.

Microcalorimetry has been used to measure the stabilities of mutational variants of yeast iso-1 cytochrome c in which F82 and L85 have been replaced by other hydrophobic amino acids. Specifically, F82 has been replaced by Y and L85 by A. The double mutant F82Y,L85A iso-1 has also been studied, and the mutational perturbations are compared to those for the two single mutants, F82Y iso-1 and L85A iso-1. Results are interpreted in terms of known crystallographic structures. The data show that (1) the destabilization of the mutant proteins is similar in magnitude to that which is theoretically predicted by the more obvious mutation-induced structural effects; (2) the free energy of destabilization of the double mutant, F82Y,L85A iso-1, is less than the sum of those of the two single mutants, almost certainly because, in the double mutant, the -OH group of Y82 is able to protrude into the cavity formed by the L85A substitution. The more favorable structural accommodation of the new -OH group in the double mutant leads to additional stability through (1) further decreases in the volumes of internal cavities and (2) formation of an extra protein-protein hydrogen bond.

Amino Acid Substitution↗
PubMed2004

Nonreplication in genetic studies of complex diseases--lessons learned from studies of osteoporosis and tentative remedies.

Inconsistent results have accumulated in genetic studies of complex diseases/traits over the past decade. Using osteoporosis as an example, we address major potential factors for the nonreplication results and propose some potential remedies. Over the past decade, numerous linkage and association studies have been performed to search for genes predisposing to complex human diseases. However, relatively little success has been achieved, and inconsistent results have accumulated. We argue that those nonreplication results are not unexpected, given the complicated nature of complex diseases and a number of confounding factors. In this article, based on our experience in genetic studies of osteoporosis, we discuss major potential factors for the inconsistent results and propose some potential remedies. We believe that one of the main reasons for this lack of reproducibility is overinterpretation of nominally significant results from studies with insufficient statistical power. We indicate that the power of a study is not only influenced by the sample size, but also by genetic heterogeneity, the extent and degree of linkage disequilibrium (LD) between the markers tested and the causal variants, and the allele frequency differences between them. We also discuss the effects of other confounding factors, including population stratification, phenotype difference, genotype and phenotype quality control, multiple testing, and genuine biological differences. In addition, we note that with low statistical power, even a "replicated" finding is still likely to be a false positive. We believe that with rigorous control of study design and interpretation of different outcomes, inconsistency will be largely reduced, and the chances of successfully revealing genetic components of complex diseases will be greatly improved.

Animals↗
PubMed1999

Genetic testing for patients with renal disease: procedures, pitfalls, and ethical considerations.

The Human Genome Project is rapidly producing insights into the molecular basis of human genetic disorders. The most immediate clinical benefit is the advent of new diagnostic methods. Molecular diagnostic tools are available for several genetic renal disorders and are in development for many more. Two general approaches to molecular diagnosis are linkage-based testing and direct mutation detection. The former is used when the gene has not been cloned but has been mapped in relation to polymorphic loci. Linkage-based testing is also helpful when a large diversity of mutations makes direct detection difficult. Limitations include the need to study multiple family members, the need for informative polymorphisms, and genetic heterogeneity. Direct mutation detection is limited by genetic heterogeneity and the need to distinguish nonpathogenic allelic variants from pathogenic mutations. Molecular testing raises a number of complex ethical issues, including those associated with prenatal or presymptomatic diagnosis. In addition, there are concerns about informed consent, privacy, genetic discrimination, and technology transfer for newly developed tests. Health professionals need to be aware of the technical and ethical implications of these new methods of testing, as well as the complexities in test interpretation, as molecular approaches are increasingly integrated into medical practice.

Ethics, Medical↗
PubMed1992

An assessment of the ability of human bone marrow cultures to generate osteoclasts.

Several groups have successfully generated osteoclasts in cultures of murine haemopoietic cells. This approach would clearly be useful in the analysis of mechanisms of regulation of human osteoclast formation if analogous results could be obtained in cultures of human bone marrow. This communication describes independent attempts by three groups to generate unequivocally defined osteoclasts from bone marrow obtained from human iliac crest, femoral neck, rib, and from foetuses. The haemopoietic tissue was incubated using techniques described by others for production of osteoclast-like cells, and with variants of this technique using strategies based on our experiences with murine osteoclastogenesis. Haemopoietic cells were incubated with calcium regulating hormones, cytokines, osteoblastic supernatants, and osteoblastic or bone marrow stromal cell layers. Formation of cells capable of excavation of bone slices was rarely seen. Despite the paucity of bone resorbing cells, multinucleate cells (MNCs) developed with similar characteristics to the MNCs that have been interpreted as osteoclast-like in human bone marrow cultures. The MNCs were, however, calcitonin-receptor (CTR) negative, and did not show the typical pattern of reactivity with osteoclast-specific antibodies. They possessed instead an antigenic profile characteristic of macrophage polykaryons. We conclude that the MNCs which consistently generate in human bone marrow cultures do not possess phenotypic characteristics specific for osteoclasts and appear to be macrophage polykaryons. The conditions required for osteoclast generation in cultures of human haemopoietic cells remain to be defined.

Bone Marrow Cells↗
PubMed1992

Localization of proliferating cell nuclear antigen (PCNA/Cyclin) in workshop cases of Hodgkin's disease and non-Hodgkin's lymphoma.

Proliferating cell nuclear antigen (PCNA/Cyclin) is a 36-kD protein that is present in cycling cells but not in resting cells, and therefore represents a marker of tumor proliferation. Application of anti-PCNA/Cyclin monoclonal antibodies has shown that this protein is localized to the nucleus of cycling cells, with the exception of cells in mitosis, which demonstrate faint cytoplasmic reactivity. Recently, Benjamin and Gown found that Reed-Sternberg cells and variants show nuclear and cytoplasmic staining with anti-PCNA/Cyclin antibody 19A2, and suggested that this feature may be useful in distinguishing Hodgkin's disease from other tumors. This report describes the reactivity of 42 workshop cases that were stained with anti-PCNA/Cyclin antibodies 19A2 and/or PC10. Thirty-three (79%) of the 42 cases showed adequate reactivity to allow for interpretation of staining localization. In the group of reactive cases, 26 (79%) showed nuclear and cytoplasmic staining. The localization of PCNA/Cyclin was compared with the consensus diagnosis in each case. Eighty percent of cases classified as Hodgkin's disease, 67% of cases classified as non-Hodgkin's lymphoma, and 100% of unresolved cases showed both nuclear and cytoplasmic staining. The incidence of cytoplasmic PCNA/Cyclin was not different between Hodgkin's disease and non-Hodgkin's lymphoma in this study.

Hodgkin Disease↗
PubMed2003

Coronary heart disease, hypertension, and angiotensinogen gene variants in Indian population.

Gene encoding components of the renin angiotensin system (RAS) have been implicated with the increased risk of cardiovascular disease (CVD). Two variants of the angiotensinogen (AGT) gene, M235T and T174M, have been shown to be associated with increased risk of hypertension. In the present study, we examined the association of these two polymorphisms and their synergistic interaction with the angiotensin I-converting enzyme (ACE) deletion homozygote genotype (D/D) on subjects with coronary heart disease (CHD) and hypertension. We studied 131 healthy individuals, 141 angiographically verified CHD patients, and 159 hypertensive subjects. The identification of the ACE and AGT gene polymorphisms was carried out using a PCR-based restriction endonuclease digestion method. There was no significant difference in the distribution of the M235T and T174M variants between the two test groups and the control group. Association was also not seen when analysis was carried out in patients when subgrouped according to the extent of the severity of the disease. In addition, the risk was not restricted to subjects carrying the D allele of the ACE gene and T235T of AGT. M235T and T174M variants do not contribute to the increased risk of CHD or hypertension in the Indian population.

Adult↗
PubMed2001

The melanocortin-1-receptor gene is the major freckle gene.

Ephelides and solar lentigines are different types of pigmented skin lesions. Ephelides appear early in childhood and are associated with fair skin type and red hair. Solar lentigines appear with increasing age and are a sign of photodamage. Both lesions are strong risk indicators for melanoma and non-melanoma skin cancer. Melanocortin-1-receptor (MC1R) gene variants are also associated with fair skin, red hair and melanoma and non-melanoma skin cancer. The purpose of this study was to investigate the relationship between MC1R gene variants, ephelides and solar lentigines. In a large case-control study, patients with melanoma and non-melanoma skin cancer and subjects without a history of skin cancer were studied. In all participants, the presence of ephelides in childhood and solar lentigines by physical examination was assessed according to strict definitions. The entire coding sequence of the MC1R gene was analyzed by single-strand conformation polymorphism analysis followed by sequence analyses. Carriers of one or two MC1R gene variants had a 3- and 11-fold increased risk of developing ephelides, respectively (both P < 0.0001), whereas the risk of developing severe solar lentigines was increased 1.5- and 2-fold (P = 0.035 and P < 0.0001), respectively. These associations were independent of skin type and hair color, and were comparable in patients with and without a history of skin cancer. The population attributable risk for ephelides to MC1R gene variants was 60%, i.e. 60% of the ephelides in the population was caused by MC1R gene variants. A dosage effect was found between the degree of ephelides and the number of MC1R gene variants. As nearly all individuals with ephelides were carriers of at least one MC1R gene variant, our data suggest that MC1R gene variants are necessary to develop ephelides. The results of the study also suggest that MC1R gene variants play a role, although less important, in the development of solar lentigines.

Adult↗
PubMed2006

UCHL-1 is not a Parkinson's disease susceptibility gene.

OBJECTIVE: The UCHL-1 gene is widely cited as a susceptibility factor for sporadic Parkinson's disease (PD). The strongest evidence comes from a meta-analysis of small studies that reported the S18Y polymorphism as protective against PD, after pooling studies of white and Asian subjects. Here, we present data that challenge this association. METHODS: In a new large case-control study in white individuals (3,023 subjects), the S18Y variant was not protective against PD under any genetic model of inheritance. Similarly, a more powerful haplotype-tagging approach did not detect other associated variants. RESULTS: Finally, in an updated S18Y-PD meta-analysis (6,594 subjects), no significant association was observed under additive, recessive, or dominant models (odds ratio = 1.00 [95% confidence interval: 0.74-1.33]; odds ratio = 1.01 [95% confidence interval: 0.76-1.35]; and odds ratio = 0.96 [95% confidence interval: 0.86-1.08], respectively), and a cumulative meta-analysis showed a trend toward a null effect. INTERPRETATION: Based on the current evidence, the UCHL-1 gene does not exhibit a protective effect in PD.

Case-Control Studies↗