Search results for "Gene mutation"
showing 10 items of 187 documents
Novel <b><i>VANGL1</i></b> Gene Mutations in 144 Slovakian, Romanian and German Patients with Neural Tube Defects
2012
Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system occurring at an average rate of 1 per 1,000 human pregnancies worldwide. Numerous genetic and environmental factors are discussed to be relevant in their etiology. In mice, mutants in >200 genes including the planar cell polarity (PCP) pathway are known to cause NTDs, and recently, heterozygous mutations in the human <i>VANGL1</i> gene have been described in a small subset of patients with NTDs. We performed a <i>VANGL1</i> mutation analysis in 144 unrelated individuals with NTDs from Slovakia, Romania and Germany and identified 3 heterozygous missense mutations: c.613…
Epidemiological study of nonsyndromic hearing loss in Sicilian newborns
2007
Deafness is caused by a variety of facts, genetic and environmental. Regarding the acquired causes, deafness can be the consequence of prenatal infections, acoustic or cerebral trauma, and the use of ototoxic drugs. Deafness can be the only manifestation (nonsyndromic forms) or it may occur together with other phenotypic findings (syndromic forms). The majority of nonsyndromicdeafness has a genetic basis [Van Camp et al., 1997]. In recent years, deafness and hearing loss have assumed a clinical importance in the study of congenital disorders [Morton et al., 1991]. The clinical interest for hearing loss is supported by the social impact that this disorder has; if not treated, delays in the d…
Detection of DNA effects in human cells with the comet assay and their relevance for mutagenesis
1996
The single cell gel test (SCG-test or comet assay) is a rapid and sensitive method for measuring DNA damage and repair in individual cells. A wide variety of mutagens have been shown to cause DNA alterations detectable with the comet assay, but it is not yet clear whether a relationship exists between the DNA effects and the induction of mutations. We are therefore investigating in a cell culture system with human cells (MRC5CV1) the induction of DNA damage by environmental mutagens and the formation of mutations at the HPRT gene. In the present study we investigated benzo[a]pyrene (BP), an environmental mutagenic and carcinogenic polycyclic aromatic hydrocarbon, and its reactive metabolite…
Biomarkers of Ineffective Erythropoiesis Predict Response to Luspatercept in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS)…
2015
Abstract Background: Luspatercept is a fusion protein (modified activin receptor IIB-IgG Fc) being investigated for the treatment of anemias with ineffective erythropoiesis. MDS patients have increased Smad2/3 signaling in the bone marrow, leading to ineffective erythropoiesis. Luspatercept inhibits Smad2/3 signaling and promotes late-stage erythroid differentiation, thereby correcting ineffective erythropoiesis. Aims: This completed, 3-month, phase 2, multicenter, open-label study evaluated the effects of luspatercept on anemia in patients with low/int-1 risk MDS (IPSS classification). Study outcomes include erythroid response of increased hemoglobin (Hb) in low transfusion burden (LTB) pa…
CFTR p.Arg117His associated with CBAVD and other CFTR-related disorders
2013
International audience; BACKGROUND:The high frequency of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutation p.Arg117His in patients with congenital bilateral absence of the vas deferens (CBAVD) and in newborns screened for CF has created a dilemma.METHODS:Phenotypic and genotypic data were retrospectively collected in 179 non-newborn French individuals carrying p.Arg117His and a second CFTR mutation referred for symptoms or family history, by all French molecular genetics laboratories, referring physicians, CF care centres and infertility clinics.RESULTS:97% of the patients had the intronic T7 normal variant in cis with p.Arg117His. 89% patients were male, wit…
Driver mutations and differential sensitivity to targeted therapies: a new approach to the treatment of lung adenocarcinoma
2010
The adenocarcinoma of the lung has recently shown peculiar molecular characteristics, which relate with both carcinogenesis and response to targeted drugs. Several molecular alterations have been defined as "driver mutations". These are responsible for both the initiation and maintenance of the malignancy. The epidermal growth factor receptor (EGFR) pathway is the main regulator of cell function and cancer development. It has a widely defined role in the occurrence of driver mutations. Up till now EGFR gene mutations, KRAS gene mutations and EML4-ALK fusion genes are the most widely recognized alterations involved in both the biology and the clinical management of lung adenocarcinoma. In th…
Cell of origin markers identify different prognostic subgroups of lung adenocarcinoma
2018
Strong prognostic markers able to stratify lung adenocarcinoma (ADC) patients are lacking. We evaluated whether a six-immunohistochemical markers panel (TTF1, SP-A, Napsin A, MUC5AC, CDX2 and CK5), defining the putative neoplastic “cell of origin,” allows to identify prognostic subgroups among lung ADC. We screened a large cohort of ADC specimens (2003–2013) from Torino Institutional Repository identifying: (i) marker positivity by immunohistochemistry, (ii) main morphological appearance by light microscopy, (iii) presence of “hotspot” mutations of candidate genes by Sequenom technology. To evaluate possible predictors of survival and time to recurrence, uni- and multivariable-adjusted comp…
High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies
2017
Item does not contain fulltext Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We performed whole-genome sequencing (WGS) in 197 individuals with unexplained DEE and pharmaco-resistant seizures and in their unaffected parents. We focused our attention on de novo mutations (DNMs) and identified candidate genes containing such variants. We sought to identify additional subjects with DNMs in these genes by performing targeted sequ…
Role of Colchicine Treatment in Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS): Real-Life Data from the AIDA Network
2020
Objective. To analyze the potential role of colchicine monotherapy in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) in terms of control of clinical and laboratory manifestations. Methods. Patients with TRAPS treated with colchicine monotherapy were retrospectively enrolled; demographic, clinical and therapeutic data were collected and statistically analysed after having clustered patients according to different times at disease onset, penetrance of mutations, dosage of colchicine, and different disease manifestations. Results. 24 patients (14 males; 15 with pediatric disease onset) treated with colchicine monotherapy were enrolled. Colchicine resulted in …
Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multice…
2018
Summary Background Encorafenib plus binimetinib and encorafenib alone improved progression-free survival compared with vemurafenib in patients with BRAF V600 -mutant melanoma in the COLUMBUS trial. Here, we report the results of the secondary endpoint of overall survival. Methods COLUMBUS was a two-part, randomised, open-label, phase 3 study done at 162 hospitals in 28 countries. Eligible patients were aged at least 18 years with histologically confirmed, locally advanced, unresectable, or metastatic cutaneous melanoma, or unknown primary melanoma, BRAF V600E or BRAF V600K mutation, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and were treatment naive or had pr…