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 199 records · Page 11Linked to original sources
PubMed1989

A lineage switch in acute monocytic leukemia. A case report.

A case of congenital monocytic leukemia that underwent a lineage switch to acute lymphocytic leukemia (ALL) is described. The original leukemia had typical monocytic features, as evidenced by morphology (FAB M5), cytochemistry (nonspecific esterase) and immunophenotype (My4 positive). Cytogenetic study showed a pseudodiploid clone t(9;11)(p22;q21) that could be interpreted as a variant of the t(9;11)(p22;q23) reported in patients with the M5 type of leukemia. After successful remission induction with single-agent chemotherapy (VM-26) and subsequent sustained remission for 12 months with alternating VM-26 and VP-16-213, lineage switch to ALL (FAB L1) occurred. The presence of both lymphoid and myeloid markers on leukemic cells at lineage switch suggested the biphenotypic character of the patient's ALL. Our observation indicates that a lineage switch can occur from monocytic leukemia to ALL, although most of the cases previously reported have been in the reverse direction. This case emphasizes again the need to carry out careful and comprehensive marker studies to gain insight into the possible prognostic significance and the application of appropriate therapy.

Bone Marrow↗
PubMed1986

[Hereditary factors and their causative role in anatomic variation].

As demonstrate the literature data and the authors' observations on the composition of the anatomical structures of the extremities at the popliteal pterigyum syndrome of Smith-Lemley-Optis, as well as at some other monogenic syndromes, the manifestation of the anatomical changeability in humans is defined, to an essential degree, by hereditary factors. A suggestion is made that investigation of the anatomical changeability in connection with genetic peculiarities of the organism makes it possible to approach the causal interpretation of the variants and the developmental anomalies and comprehend the sources of multiplicity of forms and structure of the human organs and systems.

Chromosome Aberrations↗
PubMed1988

[Biology of glucose-6-phosphate dehydrogenase deficiency].

G-6-PD deficiency is predominant in the entire history of haemolytic anemias secondary to enzyme deficiency, since its represents, by far, the most frequent erythro-enzymopathy; it is also the most studied and the best known from the clinical as well as biological standpoints. Because of the ethnic groups particularly affected, this deficiency is essentially, in France, an imported pathology, even if there are a few true european cases. The biological diagnosis of the deficient patient is simple and well codified, but the interpretation of numerous variants of the enzyme remains quite complex. The recent cloning of the gene should provide a decisive progress in understanding these various deficiencies.

Anemia, Hemolytic↗
PubMedDate not supplied

[Somatotropic function of the hypophysis in the hypothalamic puberty syndrome].

The STH level was studied in the blood of 105 patients with the hypothalamic pubertal syndrome (HPS). A tendency toward STH hyperproduction was revealed. A comparison of the STH level in the blood and the degree of obesity of the HPS patients showed a clear decrease of the growth hormone in Stage IV obesity. The STH level was almost the same in Stages I, II, III obesity. The STH secretion in the HPS patients correlated with age. The period of disease did not influence hypophysial somatotropic function in the HPS patients. No interrelationship between the content of hydrocortisone and STH in the blood was established. In most of the patients with the HPS, the growth hormone secretion in response to hypoglycemia was undisturbed. Preliminary results obtained with parlodel tests showed an opposite reaction in the HPS patients as compared to healthy ones. Our results confirmed once more that the HPS should not be interpreted as a variant of Icenko-Cushing's syndrome or constitutional obesity in which STH production was lowered.

Adolescent↗
PubMed1985

[Double-outlet right ventricle with intact interventricular septum. Case report, review of the literature and proposed pathogenetic interpretation].

Double Outlet Right Ventricle with intact ventricular septum is an extremely rare malformation. Only nine cases are recorded in the known world literature. A new case is reported, concerning a female infant six months old when first seen, and still alive after atrial septectomy. The anatomical studies in Double Outlet Right Ventricle suggest that only the Ventricular Septal Defect in the outlet septum is an integral part of the malformation and can be defined as "typical". In more than 10% of cases the Ventricular Septal Defect opens into the inlet or trabecular-muscular portions of the septum: these latter locations of the defect should therefore be considered as "associated". Double Outlet Right Ventricle with intact ventricular septum can be interpreted as the variant lacking both typical and associated Ventricular Septal Defect. From the analysis of anatomical descriptions of the ten known specimens of Double Outlet Right Ventricle with intact Ventricular septum, the Authors word out the hypothesis that ventricular septum closure could be referred to a well developed bulbo-ventricular fold (bulbo-ventricular fold synonimous of cono-ventricular flange and bulbo-atrio-ventricular ledge), as a consequence of missed or defective conal absorption. They conceive a range including on one hand the Subarterial Ventricular Septal defect (bulbo-ventricular fold poorly developed due to effective conal absorption), on the other hand the Restrictive Ventricular Septal Defect and Intact Ventricular Septum (bulbo-ventricular fold well developed due to defective conal absorption).

Female↗
PubMed1979

[Impetigo herpetiformis and PUVA-treatment (author's transl)].

Report on a 20 years old pregnant woman, who fulfilled the criteria of the impetigo herpetiformis as well as later those of the pustular psoriasis Zumbusch in her clinical course. The impetigo herpetiformis is interpreted as a variant of the pustular psoriasis occurring during the pregnancy with lowered calcium-level, which increases the endogeneous eruption pressure. After negative attempts of treatment with Prednisolon, antibiotics, and later with Methotrexat an excellent therapeutic effect could be achieved by oral PUVA-treatment.

Administration, Oral↗
PubMed1980

[Delusional psychopathology of the paranoid stage of paranoid schizophrenia].

The psychopathological traits of paranoial delusions were studied in 65 patients with paranoial schizophrenia. Of these patients, 16 had hypochondriacal delusions, 13 delusions of jealousy and 36 delusions of reference and persecution. All cases were studied from the standpoint of structural-dynamic aspects of the development of systematized interpretative delusions. Two variants of the development of such delusions were distinguished: paranoic and mixed. The paranoic variant by its nature appeared to be catathymic (4 cases), in a mixed variant separate elements of sensorial and imaginative delusions were interspersed with a catathymic development of delusions. Such states were mainly expressed in the form of delusions of significance and special significance. An assumption is made that there is a reciprocal transition of catathymic delusions, delusions of significance and special significance in compliance to the development of the morbid process.

Adolescent↗
PubMedDate not supplied

[Polycystosis of the brain].

This paper presents a case with 11-year history of disseminated cerebral polycystosis in a 23-year-old female. Physical examination and CT, MRT, histological and biochemical data suggest that the disease is morphologically progressive; however, the spread on brain lesions showed no correlation with relatively mild clinical manifestations of the disease. Variants of nosological interpretation of histological data are discussed.

Adult↗
PubMed2025

Extracting and calibrating evidence of variant pathogenicity from population biobank data.

Genomic medicine requires a robust evidence base of variant phenotypic impacts, which remains incomplete even in extensively studied genes with monogenic disease associations. Here, we evaluated the broad potential of using population cohort data to identify evidence that can be used in variant assessment. Across 41 genes related to 18 clinically actionable monogenic phenotypes, we calculated variant-level odds ratios of disease enrichment using data from 469,803 UK Biobank participants. We found significant differences in odds ratio values between ClinVar-labeled pathogenic and benign variants in 11 phenotypes, spanning both common and rare disorders. To facilitate clinical translation, we calibrated the strength of evidence provided by variant-level odds ratios to align with American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) interpretation guidelines (PS4 criterion) and found that odds ratios may reach "moderate," "strong," or "very strong" evidence, varying by phenotype and gene. Overall, we found that 2.6% (N = 12,350) of participants harbor a rare variant of uncertain significance (VUS) with at least moderate evidence of pathogenicity-an indication of potentially unrecognized disease risk. Finally, by incorporating computational and functional data alongside population-based odds ratios, we identified variants that met the criteria for clinical reclassification. Notably, using this approach, we identified that 12.4% of rare VUSs in LDLR seen in participants meet diagnostic criteria to be classified as likely pathogenic, demonstrating its potential to scale the reclassification of VUSs.

Humans↗
PubMed2003

[Disease-causing mutations versus neutral polymorphism: use of bioinformatics and DNA diagnosis].

Molecular genetic diagnostics is available for increasing number of genetically determined diseases. A wide spectrum of mutations can be detected by laboratory methods. A mutation can be defined as a change in a specific DNA sequence when compared with the reference sequence published in the gene database. However, in some cases it is difficult to distinguish if the detected sequence variant is a causal mutation or a neutral (polymorphic) variation without any effect on phenotype. The interpretation of rare sequence variants of unknown significance detected in disease-causing genes becomes an increasingly important problem. Further analysis on DNA and on protein levels with the use of bioinformatics are needed to reveal the effect of rare sequence variants. Inherited complex disorders, for example rare hereditary forms of cancer diseases, represent a challenge to molecular geneticists. The identification of exact causal mutation directly responsible for the development of the disease and for the assessment of disease risk resulting from this genetic variation has further implications. Predictive genetic diagnostics allows identify relatives at high risk of genetically determined disease and use of targeted preventive and therapeutic approaches. In severe cases it allows also prenatal or pre-implantation diagnostics.

DNA Mutational Analysis↗
PubMed1985

[Clinico-psychopathologic varieties of the acute Kandinsky-Clerambault syndrome in schizophrenia].

Acute cases of the Kandinsky-Clerambault syndrome first manifested in adulthood were studied in schizophrenic patients. On the basis of the clinical mechanisms of the development of psychosis and the specific features of acute delirious disturbances in the structure of psychosis 3 clinical variants of the acute syndrome of psychic automatism were identified: developing according to the type of reaction in the structure of acute paranoid (the first variant), according to the regularities of endogenic paroxysm in the picture of acute sensory delirium (the second variant) and according to the mechanism of exacerbation of chronic delirium entering the structure of acute interpretative delirium (the third variant).

Acute Disease↗
PubMed2004

Polymorphisms in factor II and factor VII genes modulate oral anticoagulation with warfarin.

BACKGROUND AND OBJECTIVES: There is very considerable inter-individual variability in warfarin dosages necessary to achieve target therapeutic anticoagulation. The variability is largely genetically determined but can only partly be explained by genetic variability in the cytochrome CYP2C9 locus. Polymorphisms within the genes coding for vitamin K-dependent proteins have been suggested to predict sensitivity to warfarin therapy. DESIGN AND METHODS: In a cohort of 147 patients followed-up at one specialized clinic from the start of anticoagulation with warfarin, we investigated whether factor II (Thr165Met; G20210A) and factor VII polymorphisms (G-402A; G-401T) affected the doses of warfarin necessary to acquire the target intensity of anticoagulation. RESULTS: Regardless of the presence of confounding variables, the mean adjusted dose of warfarin required was higher among patients with the factor II Thr/Thr 165 genotype (4.2 mg) than among patients carrying the Met165 allele (2.9 mg; p=0.041) and higher in carriers of the factor VII GG-401 genotype (4.1 mg) than in those with the T-401 allele (3.1 mg; p=0.029). No significant effect was found for factor II A20210G and factor VII G-402A polymorphisms. All together, the genetic variants investigated accounted for about a quarter (r2: 0.261) of the inter-individual variability calculated in the present setting. INTERPRETATION AND CONCLUSIONS: Genetic variants of factor II and factor VII modulate the mean daily dose of warfarin required to achieve a target intensity of anticoagulation.

Administration, Oral↗
PubMed2006

Effect of NOD2/CARD15 variants in T-cell depleted allogeneic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Three single nucleotide polymorphisms (SNP) in the NOD2/CARD15 gene have been associated with the incidence and the severity of acute graft-versus-host disease (GVHD) following allogeneic stem cell transplantation (SCT). We hypothesized that the clinical effect of SNP in NOD2/CARD15 might be different in patients submitted to T-cell-depleted allogeneic SCT, in which donor T cells, the main effectors of GVHD, are eliminated. DESIGN AND METHODS: SNP 8, 12 and 13 in NOD2/CARD15 were studied using a Taqman protocol in 85 patients undergoing HLA-identical, T-cell-depleted SCT and in 71 of their sibling donors. RESULTS: NOD2/CARD15 variants were present in nine (11%) patients and six (8%) donors. The incidences of acute GVHD and chronic GVHD were not associated with either the donors' or recipients' NOD2/CARD15 variants. In contrast, these genetic variants were associated with a lower disease-free survival (17% vs. 48%, p=0.03). Death due to pulmonary infection was more frequent in the group of patients with NOD2/CARD15 variants. In the multivariate analysis, only NOD2/CARD15 variants (RR 2.3, p=0.04) and older age (RR 2.2; p=0.04) were independent prognostic factors for disease-free survival. INTERPRETATION AND CONCLUSIONS: NOD2/CARD15 variants have a deleterious effect on clinical outcome in T-cell-depleted allogeneic SCT, which is independent of GVHD. These results supports the hypothesis that the detrimental effect of NOD2/CARD15 variants in such a transplant setting might be produced by an alteration of the innate immune system more than by activation of the adaptive immune system.

Adult↗
PubMed2003

[Solitary fibrous pseudopapillary tumor of the lung: pulmonary fibroadenoma and adenofibroma revisited].

We describe a peculiar pulmonary lesion, that we interpreted as a pseudopapillary variant of solitary fibrous tumor. The patient was a 62-year-old asymptomatic male, non smoking, presenting with a peripheral nodule, 0.8 cm across, located in the lower lobe of the right lung. The patient is alive and well 18 months after surgical excision of the nodule. Microscopically, the lesion was well-circumscribed and characterized by a diffuse pseudopapillary pattern. Pseudopapillae were large, and were covered by a rim of cubic epithelium devoid of atypia. The stromal axis was fibrous and contained scattered bland spindle cells. Immunohistochemically, the latter were strongly positive for vimentin and CD34, focally positive for BCL2 and CD99, negative for cytokeratin, EMA, TTF1, calretinin, smooth muscle actin, desmin and S100 protein; the epithelial cells were immunoreactive for cytokeratin, EMA and TTF1. We interpret this lesion as a peculiar pseudopapillary variant of solitary fibrous tumor, corresponding to what has been reported in the literature as pulmonary adenofibroma and fibroadenoma. The most important differential diagnostic considerations are briefly discussed.

Adenofibroma↗
PubMedDate not supplied

[Ultrasonographic evaluation of the thyroid palpation method in determining its dimensions in children and adolescents].

The authors analyze the diagnostic value of thyroid palpation method (two modifications) comparing its results with those of ultrasonographic volumetry. The study involved 118 children aged 5 and 14 of both sexes living in regions endemic for goiter. The thickness of thyroid isthmus was found virtually the same no matter how greatly the gland was enlarged. The results proved the necessity of age-specific corrections in the criteria of current interpretation of palpation data: the first degree in preschool children was most often indicative of thyroid hypertrophy whereas in the pubertal age it was just a variant of normal size. Interpretation with due account of these amendments improved the reliability of diagnostic value of palpation, its sensitivity being 63 +/- 6, specificity 67 +/- 6, and accuracy 65 +/- 4%. When the results of palpation are adequately interpreted, the examinees' age and sex and the method of examination proper do not influence the data accuracy. The sensitivity of palpation in detection of nodules up to 10 mm in diameter proved to be null (in 6 of the 81 examined adolescents sonographic signs of encapsulated formation were seen in the thyroid). Bearing all this in mind, the authors discuss differentiated approaches to management of children and adolescents with the first degree of palpated enlargement of the thyroid.

Adolescent↗
PubMed2004

Universal nuclear spin relaxation and long-range order in nematics strongly confined in mass fractal silica gels.

We show how the low-frequency dependence of the proton spin-lattice relaxation time T1(nu) of octylcyanobiphenyl liquid crystals confined in high-density silica gels evidences a long-range order nematic phase in spite of the strong confinement and random disorder of the gels. The universal value and frequency dependence observed, T1(nu) proportional, variant nu(2/3), is interpreted within a relaxation model due to director fluctuations in nematic liquid crystals confined to mass fractal porous media. The model provides a relation T1(nu) proportional, variant nu(2-d/2), giving a reliable value of the structural fractal dimension d(f)=2.67 for all the host silica gels.

Journal Article↗
PubMed2002

Electrospray tandem mass spectrometry of intact beta-chain hemoglobin variants.

In this report, we present data to illustrate how human hemoglobin (Hb) variants can be identified by electrospray tandem mass spectrometry (MS/MS) of the intact Hb chains following the one-step dilution of whole blood. MS/MS spectra were recorded on a series of intact beta-chain human Hb variants. The resultant spectra were interpreted, and using the information gleaned from the fragmentation patterns of known variants, two unknown beta-chain variants were characterized solely by this mass spectrometric method. Fragment ions that serve to identify beta-chain variants were identified. The fragmentation patterns of the intact beta-chain [M + 18H]18+ ions showed classical facile cleavages adjacent to acidic residues and N-terminal to proline residues, with Thr50-Pro51 being the most prominent cleavage site. Abundant product ions were formed by peptide bond cleavage in the regions close to the termini of the beta chain, the central region being less well-represented in the MS/MS spectra. Nearly 50% of the beta-chain primary structure could be determined by MS/MS of the intact chain. However, analysis of the Hb variants where mutations have occurred in the inner region (residues 58-111) of the beta globin proved to be difficult and required mass spectrometric analysis of their tryptic peptides for a complete identification.

Genetic Variation↗
PubMed1992

Pseudosubluxation of C2-C3 in childhood: a frequent clinico-radiological diagnostic error.

Although serious cervical injuries in pediatric patients are very infrequent, the may occur occasionally as a result of a strong blow to the head. Clinical records and radiological pictures, and in some cases computer tomography, help to provide the correct diagnosis. During childhood there are several normal radiological variants that may be interpreted as pathological findings, of which pseudosubluxation C2-C3 is the most frequent. We present two such cases and discuss the clinical and radiological criteria for the differential diagnosis between normal variants and injuries to the cervical spine in pediatric patients.

Adolescent↗