Search results for " Mutation"
showing 10 items of 1212 documents
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.
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…
β-Catenin Activation Regulates Tissue Growth Non–Cell Autonomously in the Hair Stem Cell Niche
2014
Coordinated Hair Growth Wnt/β-catenin signaling is a key pathway that plays a conserved role in regulating stem cell function during adult tissue regeneration. Using time-lapse imaging of live mice, Deschene et al. (p. 1353 ) show that genetic activation of β-catenin within hair follicle stem cells generates axes of hair growth by coordinated cell divisions and cell movements, even when the normal niches—the dermal papillae—are laser-ablated. Activated β-catenin enhances Wnt ligand secretion, and these ligands can then activate Wnt signaling in adjacent cells that do not have activated β-catenin, indicating how activated stem cells could influence neighboring cells during normal growth and …
Elusive amines and cluster headache: mutational analysis of trace amine receptor cluster on chromosome 6q23.
2004
Cluster headache (CH) is characterised by unilateral pain and ipsilateral autonomic features. To date, no molecular genetic evidence has been shown for CH. Small pedigrees and low penetrance render the identification of the CH-gene quite difficult. Nonetheless the association of CH and migraine to a new class of amine, namely trace or elusive amines such as tyramine, octopamine and synephrine, has recently been demonstrated. In particular, in comparison to healthy control subjects, all these neurotransmitters have been found to be greatly elevated in CH sufferers in plasma and platelets both in active and remission periods. A cluster of gene-encoding G-protein-coupled receptors that bind an…
Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas
2007
AbstractIntegrative genomic and gene-expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene-expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them w…
First case in Italy of acquired resistance to oseltamivir in an immunocompromised patient with influenza A/H1N1v infection
2010
A pandemic influenza A/H1N1v strain with the neuraminidase H274Y mutation was detected in nasal secretions of a 2-year-old leukemic patient with influenza-like illness after 18 days of treatment with oseltamivir. At baseline, no drug-resistant virus was found, while 4 days after treatment initiation a mix- ture of wild-type and mutated virus was detected. After treatment interruption, the wild type influenza virus re-emerged and became prevalent in nasal secretions after a few days, suggesting the lower fitness of the mutated virus strain. The patient slowly improved concurrently with a decrease in virus load, which resulted negative 42 days after diagnosis. No other drug-resistant influenz…
Phenotype/Genotype Relationship in Left Ventricular Noncompaction: Ion Channel Gene Mutations Are Associated With Preserved Left Ventricular Systolic…
2021
International audience; Background: Few data exist concerning genotype-phenotype relationships in left ventricular noncompaction (LVNC).Methods and results: From a multicenter French Registry, we report the genetic and clinical spectrum of 95 patients with LVNC, and their genotype-phenotype relationship. Among the 95 LVNC, 45 had at least 1 mutation, including 14 cases of mutation in ion channel genes. In a complementary analysis including 16 additional patients with ion channel gene mutations, for a total of 30 patients with ion channel gene mutation, we found that those patients had higher median LV ejection fraction (60% vs 40%; P < .001) and more biventricular noncompaction (53.1% vs 18…
Cylindromatosis (Cyld) gene mutation in T cells promotes the development of an IL-9-dependent allergic phenotype in experimental asthma
2016
Cylindromatosis (CYLD) is a ubiquitously expressed deubiquitinating enzyme which removes activating ubiquitin residues from important signaling molecules of the NF-κB pathway. In CYLDex7/8 transgenic mice, a naturally occurring short isoform (sCYLD) is overexpressed in the absence of full length CYLD, leading to excessive NF-κB activity. Herein, we investigated the impact of the CYLDex7/8 mutation selectively in T cells on the development of experimental allergic airway disease induced by sensitization and challenge with ovalbumin. Compared with their wildtype littermates, mice bearing the T cell-specific mutation (CD4+CYLDex7/8) display stronger eosinophilia and mucus production in the lun…