Search results for "MUTATION"
showing 10 items of 2830 documents
The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder
2022
De novo variants in QRICH1 (Glutamine-rich protein 1) has recently been reported in 11 individuals with intellectual disability. The function of QRICH1 is largely unknown but it is likely to play a key role in the unfolded response of endoplasmic reticulum (ER) stress through transcriptional control of proteostasis. In this study, we present 27 additional individuals and delineate the clinical and molecular spectrum of the individuals (n=38) with QRICH1 variants. The main clinical features were mild to moderate developmental delay/intellectual disability (71%), non-specific facial dysmorphism (92%) and hypotonia (39%). Additional findings included poor weight gain (29%), short stature (29%)…
Azole-resistant Aspergillus fumigatus: A global phenomenon originating in the environment?
2019
Abstract Aspergillus fumigatus is the predominant etiological agent of invasive aspergillosis (IA), a difficult-to-manage fungal disease associated with a high case fatality rate. Azole antifungals, particularly voriconazole, have significantly improved the survival rate of patients with IA. However, the clinical advances made possible through the use of medical azoles could be threatened by the emergence of azole-resistant strains which has been reported in an ever-increasing number of countries over the last 10 years. The major resistance mechanism, that combines point mutation(s) in the coding sequence of cyp51A gene and an insertion of a tandem repeat in the promoter region of this gene…
Translational readthrough of ciliopathy genes BBS2 and ALMS1 restores protein, ciliogenesis and function in patient fibroblasts
2021
Abstract Background Ciliary dysfunction underlies a range of genetic disorders collectively termed ciliopathies, for which there are no treatments available. Bardet-Biedl syndrome (BBS) is characterised by multisystemic involvement, including rod-cone dystrophy and renal abnormalities. Together with Alstrom syndrome (AS), they are known as the ‘obesity ciliopathies’ due to their common phenotype. Nonsense mutations are responsible for approximately 11% and 40% of BBS and AS cases, respectively. Translational readthrough inducing drugs (TRIDs) can restore full-length protein bypassing in-frame premature termination codons, and are a potential therapeutic approach for nonsense-mediated ciliop…
Cutaneous mosaic syndromes associated with early postzygotic activating BRAF mutations
2017
IF 3.528; International audience
A non common BRAF mutation c1799-1801 delTGA identified in sporadic colon rectal cancer of sicilian patients
2010
Anthracycline has been shown to induce heart failure. To monitor this toxic damage, echocardiographic parameters of left ventricular (LV) systolic function are usually used. Aim of this study was to evaluate in lymphoma’s patients the reliability of echocardiographic data in comparison with a LV systo-diastolic parameter function: the Tei index.
BRAFV600E MUTATION, TISSUE INHIBITOR OF METALLOPROTEINASE-1 UPREGULATION AND NF-KB ACTIVATION: CLOSING THE LOOP ON THE PAPILLARY THYROID CANCER TRILO…
2011
BRAFV600E is the most common mutation in papillary thyroid carcinoma (PTC). Tissue inhibitor of metalloproteinases (TIMP-1) and Nuclear Factor (NF)-kB have been shown to play an important role in thyroid cancer. Our aim was to evaluate whether an interplay among these three factors exerts a functional role in PTCs. 56 PTC specimens were analyzed for BRAFV600E mutation, TIMP-1 expression and NF-kB activation by real-time allele-specific amplification, realtime quantitative PCR (qRT-PCR) and electroforetic mobility shift assay (EMSA), respectively. We show that BRAFV600E mutation occurs selectively in PTC nodules and determines up-regulation of TIMP-1 and hyperactivation of NF-kB. In addition…
BRCA1/2 variants of unknown significance in hereditary breast and ovarian cancer (HBOC) syndrome: Looking for the hidden meaning
2021
Hereditary breast and ovarian cancer syndrome is caused by germline mutations in BRCA1/2 genes. These genes are very large and their mutations are heterogeneous and scattered throughout the coding sequence. In addition to the above-mentioned mutations, variants of uncertain/unknown significance (VUSs) have been identified in BRCA genes, which make more difficult the clinical management of the patient and risk assessment. In the last decades, several laboratories have developed different databases that contain more than 2000 variants for the two genes and integrated strategies which include multifactorial prediction models based on direct and indirect genetic evidence, to classify the VUSs a…
Pathogenic correlation between mosaic variegated aneuploidy 1 (MVA1) and a novel BUB1B variant: a reappraisal of a severe syndrome.
2022
Funder: Università degli Studi di Catania
The Agr communication system provides a benefit to the populations of Listeria monocytogenes in soil
2014
International audience; In this study, we investigated whether the Agr communication system of the pathogenic bacterium Listeria monocytogenes was involved in adaptation and competitiveness in soil. Alteration of the ability to communicate, either by deletion of the gene coding the response regulator AgrA (response-negative mutant) or the signal pro-peptide AgrD (signal-negative mutant), did not affect population dynamics in soil that had been sterilized but survival was altered in biotic soil suggesting that the Agr system of L. monocytogenes was involved to face the complex soil biotic environment. This was confirmed by a set of co-incubation experiments. The fitness of the response-negat…
Electrophysiological evidence for heptameric stoichiometry of ion channels formed by Staphylococcus aureus alpha-toxin in planar lipid bilayers.
2000
Staphylococcal alpha-toxin forms homo-oligomeric channels in lipid bilayers and cell membranes. Here, we report that electrophysiological monitoring of single-channel function using a derivatized cysteine substitution mutant allows accurate determination of the subunit stoichiometry of the oligomer in situ. The electrophysiological phenotype of channels formed in planar lipid bilayers with the cysteine replacement mutant I7C is equal to that of the wild type. When pores were formed with I7C, alterations of several channel properties were observed upon modification with SH reagents. Decreases in conductance then occurred that were seen only as negative voltage was applied. At the level of si…