Search results for " Gene Deletion"
showing 10 items of 11 documents
The severe phenotype of Diamond-Blackfan anemia is modulated by heat shock protein 70.
2017
International audience; Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome that exhibits an erythroid-specific phenotype. In at least 70% of cases, DBA is related to a haploinsufficient germ line mutation in a ribosomal protein (RP) gene. Additional cases have been associated with mutations in GATA1. We have previously established that the RPL11+/Mut phenotype is more severe than RPS19+/Mut phenotype because of delayed erythroid differentiation and increased apoptosis of RPL11+/Mut erythroid progenitors. The HSP70 protein is known to protect GATA1, the major erythroid transcription factor, from caspase-3 mediated cleavage during normal erythroid differentiation.…
Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood.
2021
Postzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of p…
Interaction of wild-type and naturally occurring deleted variants of hepatitis B virus core polypeptides leads to formation of mosaic particles
2000
AbstractThe simultaneous presence of hepatitis B virus (HBV) genomes carrying wild-type (wt) and in-frame deleted variants of the HBV core gene has been identified as a typical feature of HBV-infected renal transplant patients with severe liver disease. To investigate possible interactions of wt and deleted core polypeptides a two-vector Escherichia coli expression system ensuring their concomitant synthesis has been developed. Co-expression of wt and a mutant core lacking 17 amino acid residues (77–93) within the immunodominant region led to the formation of mosaic particles, whereas the mutant alone was incapable of self-assembly.
p16INK4A (CDKN2A) gene deletion is a frequent genetic event in synovial sarcomas.
2006
We assessed the frequency of genomic deletion of p16 INK4A (CDKN2A) in synovial sarcomas (SSs) and its possible association with immunoexpression of p16 and cyclin D1 and the Ki-67 proliferation index using dualcolor fluorescence in situ hybridization (FISH) on tissue microarray sections of 41 histologically and molecularly confirmed SSs. A heterozygous p16 INK4A gene deletion was identified in 28 (74%) of 38 cases, with 25 (89%) of them showing abnormal p16 protein expression (20 negative and 5 heterogeneous). Of 25 cases, 19 (76%) exhibiting increased cyclin D1 expression also demonstrated heterozygous p16 INK4A deletion. No significant association was observed between p16 INK4A deletion …
Enhanced proinflammatory response to the Candida albicans gpi7 null mutant by murine cells.
2008
International audience; The Candida albicans gpi7/gpi7 null mutant strain (Deltagpi7), which is affected in glycosylphosphatidylinositol (GPI) anchor biosynthesis, showed a reduced virulence following systemic infection of C57BL/6 mice. In vitro production of TNF-alpha, IL-6 and IL-1beta by macrophages in response to Deltagpi7 cells was significantly increased as compared to control (wild type GPI7/GPI7 and revertant gpi7/GPI7) cells; this probably contributes to the enhanced recruitment of neutrophils to the peritoneal cavity in response to Deltagpi7 cells. Survival of knockout mice for Toll-like receptor (TLR) 2 and TLR4 following intravenous injection of Deltagpi7 cells showed no signifi…
Toxicity of ligand-dependent Cre recombinases and generation of a conditional Cre deleter mouse allowing mosaic recombination in peripheral tissues.
2007
Ligand-activated Cre recombinases are widely used for studying gene function in vitro and in conditional mouse models. To compare ligand-dependent Cre recombinases, different Cre estrogen receptor fusions were introduced into the ROSA26 locus of embryonic stem (ES) cells and assayed for genotoxicity and recombination efficiency. Of the tested recombinases, the CreERT2 variant showed no toxicity and was highly responsive to ligand induction. To constitutively express CreERT2 in mice and also to clarify whether the CreERT2 system displays background activity, we generated a knock-in mouse line harboring the CreERT2 coding region under the control of the ROSA26 locus. Analysis of this ROSA26-…
Hypertrophic pyloric stenosis masked by kidney failure in a male infant with a contiguous gene deletion syndrome at Xp22.31 involving the steroid sul…
2022
Abstract Background Contiguous gene deletion syndrome at Xp22.3 resulting in nullisomy in males or Turner syndrome patients typically encompasses the steroid sulfatase gene (STS) and contiguously located other genes expanding the phenotype. In large deletions, that encompass also the Kallmann syndrome 1 gene (KAL1), occasionally infantile hypertrophic pyloric stenosis (IHPS) and congenital anomalies of the kidney and urinary tract (CAKUT) have been reported. Patient presentation We report on a male newborn with family history in maternal uncle of renal abnormalities and short stature still without ichthyosiform dermatosis. The baby presented CAKUT with kidney failure and progressive vomitin…
Presence of calreticulin mutations in JAK2-negative polycythemia vera
2014
Abstract Calreticulin (CALR) mutations have recently been reported in JAK2- and MPL-negative Myeloproliferative Neoplasms (MPN), particularly essential thrombocythemia (ET) and primary myelofibrosis (PMF).The clinical course of sporadic CALR-mutated patients seems to be more indolent than that of JAK2-mutated patients. In contrast, no CALR mutation has been found in the 647 published cases of Polycythemia Vera (PV) patients tested. Consequently, CALR mutations were considered exclusive to JAK2 and MPL mutations. Since 98% of PV patients harbor a JAK2 mutation (mostly the V617F mutation in exon 14 and more rarely, in exon 12), the absence of CALR mutations in PV seemed logical. Here, we desc…
A role for the peroxisomal 3-ketoacyl-CoA thiolase B enzyme in the control of PPARα-mediated upregulation of SREBP-2 target genes in the liver.: ThB …
2011
International audience; Peroxisomal 3-ketoacyl-CoA thiolase B (Thb) catalyzes the final step in the peroxisomal β-oxidation of straight-chain acyl-CoAs and is under the transcription control of the nuclear hormone receptor PPARα. PPARα binds to and is activated by the synthetic compound Wy14,643 (Wy). Here, we show that the magnitude of Wy-mediated induction of peroxisomal β-oxidation of radiolabeled (1-(14)C) palmitate was significantly reduced in mice deficient for Thb. In contrast, mitochondrial β-oxidation was unaltered in Thb(-/-) mice. Given that Wy-treatment induced Acox1 and MFP-1/-2 activity at a similar level in both genotypes, we concluded that the thiolase step alone was respons…
Clinical Significance of Rare Copy Number Variations in Epilepsy A Case-Control Survey Using Microarray-Based Comparative Genomic Hybridization
2012
Objective To perform an extensive search for genomic rearrangements by microarray-based comparative genomic hybridization in patients with epilepsy. Design Prospective cohort study. Setting Epilepsy centers in Italy. Patients Two hundred seventy-nine patients with unexplained epilepsy, 265 individuals with nonsyndromic mental retardation but no epilepsy, and 246 healthy control subjects were screened by microarray-based comparative genomic hybridization. Main Outcomes Measures Identification of copy number variations (CNVs) and gene enrichment. Results Rare CNVs occurred in 26 patients (9.3%) and 16 healthy control subjects (6.5%) (P = .26). The CNVs identified in patients were larger (P = …