MoaB2, a newly identified transcription factor, binds to σ in .

In mycobacteria, σ is the primary sigma factor. This essential protein binds to RNA polymerase (RNAP) and mediates transcription initiation of housekeeping genes. Our knowledge about this factor in mycobacteria is limited.

Diagnosis, treatment, and surveillance of Diamond-Blackfan anaemia syndrome: international consensus statement.

Diamond-Blackfan anaemia (DBA), first described over 80 years ago, is a congenital disorder of erythropoiesis with a predilection for birth defects and cancer. Despite scientific advances, this chronic, debilitating, and life-limiting disorder continues to cause a substantial physical, psychological, and financial toll on patients and their families. The highly complex medical needs of affected patients require specialised expertise and multidisciplinary care.

The alternative sigma factor SigN of is intrinsically toxic.

Sigma factors bind and direct the RNA polymerase core to specific promoter sequences, and alternative sigma factors direct transcription of different regulons of genes. Here, we study the pBS32 plasmid-encoded sigma factor SigN of to determine how it contributes to DNA damage-induced cell death. We find that SigN causes cell death when expressed at high levels and does so in the absence of its regulon suggesting it is intrinsically toxic.

Elevated erythroferrone distinguishes erythrocytosis with inherited defects in oxygen-sensing pathway from primary familial and congenital polycythaemia.

Congenital erythrocytoses represent a heterogenous group of rare defects of erythropoiesis characterized by elevated erythrocyte mass. We performed molecular-genetic analysis of 21 Czech patients with congenital erythrocytosis and assessed the mutual link between chronic erythrocyte overproduction and iron homoeostasis. Causative mutations in erythropoietin receptor (EPOR), hypoxia-inducible factor 2 alpha (HIF2A) or Von Hippel-Lindau (VHL) genes were detected in nine patients, including a novel p.

The Pyruvate Kinase Deficiency Global Longitudinal (Peak) Registry: rationale and study design.

Introduction: Pyruvate kinase (PK) deficiency is a rare, under-recognised, hereditary condition that leads to chronic haemolytic anaemia and potentially serious secondary complications, such as iron overload, cholecystitis, pulmonary hypertension and extramedullary haematopoiesis. It is an autosomal recessive disease caused by homozygous or compound heterozygous mutations in the gene. Due to its rarity and clinical heterogeneity, information on the natural history and long-term clinical course of PK deficiency is limited, presenting major challenges to patient management, the development of new therapies and establishing disease-specific treatment recommendations.

Missense mutation in RPS7 causes Diamond-Blackfan anemia via alteration of erythrocyte metabolism, protein translation and induction of ribosomal stress.

Diamond-Blackfan anemia (DBA) is predominantly underlined by mutations in genes encoding ribosomal proteins (RP); however, its etiology remains unexplained in approximately 25 % of patients. We previously reported a novel heterozygous RPS7 mutation hg38 chr2:g.3,580,153G > T p.

The Glucocorticoid Receptor Polymorphism Landscape in Patients With Diamond Blackfan Anemia Reveals an Association Between Two Clinically Relevant Single Nucleotide Polymorphisms and Time to Diagnosis.

NR3C1, the gene encoding the glucocorticoid receptor, is polymorphic presenting numerous single nucleotide polymorphisms (SNPs) some of which are emerging as leading cause in the variability of manifestation and/or response to glucocorticoids in human diseases. Since 60-80% of patients with Diamond Blackfan anemia (DBA), an inherited pure red cell aplasia induced by mutations in ribosomal protein genes became transfusion independent upon treatment with glucocorticoids, we investigated whether clinically relevant NR3C1 SNPs are associated with disease manifestation in DBA. The eight SNPs rs10482605, rs10482616, rs7701443, rs6189/rs6190, rs860457, rs6198, rs6196, and rs33388/rs33389 were investigated in a cohort of 91 European DBA patients.

Myopic Correction with Iris-Fixated Phakic Intraocular Lenses: Twelve-Year Results.

Purpose: To evaluate a 12-year follow-up of myopic patients after iris-fixated phakic intraocular lenses (IF pIOLs) implantation. . Ophthalmology Department, Military University Hospital in Prague (Czech Republic).

Oxidative DNA Damage, Inflammatory Signature, and Altered Erythrocytes Properties in Diamond-Blackfan Anemia.

Molecular pathophysiology of Diamond-Blackfan anemia (DBA) involves disrupted erythroid-lineage proliferation, differentiation and apoptosis; with the activation of p53 considered as a key component. Recently, oxidative stress was proposed to play an important role in DBA pathophysiology as well. CRISPR/Cas9-created Rpl5- and Rps19-deficient murine erythroleukemia (MEL) cells and DBA patients' samples were used to evaluate proinflammatory cytokines, oxidative stress, DNA damage and DNA damage response.

Importance of Hepcidin in the Etiopathogenesis of Anemia in Inflammatory Bowel Disease.

Anemia is the most common extraintestinal systemic complication of inflammatory bowel disease. Iron deficiency anemia and anemia of chronic disease are among the most frequent types. Intestinal iron absorption is controlled by the activity of ferroportin.

Severe linezolid-induced lactic acidosis in a child with acute lymphoblastic leukemia: A case report.

Linezolid is an antibiotic increasingly used for treatment of resistant Gram-positive infections, which blocks bacterial proteosythesis through direct inhibition of mitochondrial ribosomes. The most common adverse effects of linezolid include gastrointestinal symtoms, peripheral neuropathy, bone marrow depression and lactic acidosis. Here we present a rare case of a 9-year-old female, a survivor of acute lymphoblastic leukemia (ALL) and a hematopoietic stem cell transplant (HSCT), who developed life-threatening lactic acidosis with vomiting, impaired consciousness and Kussmaul breathing after 51 days of intravenous linezolid administration due to mycobacterial infection.

Genotype-phenotype association and variant characterization in Diamond-Blackfan anemia caused by pathogenic variants in .

Diamond Blackfan anemia (DBA) is predominantly an autosomal dominant inherited red cell aplasia primarily caused by pathogenic germline variants in ribosomal protein genes. DBA due to pathogenic RPL35A variants has been associated with large 3q29 deletions and phenotypes not common in DBA. We conducted a multi-institutional genotype-phenotype study of 45 patients with DBA associated with pathogenic RPL35A germline variants and curated the variant data on 21 additional cases from the literature.

Czech and Slovak Diamond-Blackfan Anemia (DBA) Registry update: Clinical data and novel causative genetic lesions.

Diamond-Blackfan anemia (DBA) is a rare congenital erythroid aplasia, underlied by haploinsufficient mutations in genes coding for ribosomal proteins (RP) in approximately 70% of cases. DBA is frequently associated with somatic malformations, endocrine dysfunction and with an increased predisposition to cancer. Here we present clinical and genetic characteristics of 62 patients from 52 families enrolled in the Czech and Slovak DBA Registry.

Changes in serum hepcidin levels in children with inflammatory bowel disease during anti-inflammatory treatment.

Aim: The aim of this study was to compare changes in serum hepcidin levels in paediatric patients with inflammatory bowel disease during therapy and correlate them with markers of iron metabolism, inflammation and type of treatment.

Methods: Children with newly diagnosed Crohn's disease (CD) and ulcerative colitis (UC) were included in this longitudinal study. Blood and stool samples were collected to assess levels of serum hepcidin and markers of iron metabolism parameters and inflammation.

[Rare anemias from the group of congenital bone marrow failure syndromes].

This review summarizes the pathophysiology, genetic background and clinical symptoms of anemias belonging to the group of inherited bone marrow failure syndromes with unilineage failure of erythropoiesis. It sums up the current knowledge of three diseases: Diamond-Blackfan anemia, congenital dyserythropoietic anemia and Fanconi anemia whose pathophysiology was elucidated in detail during the last decade, owing to the rapid development of new molecular-genetic techniques, especially next-generation sequencing. Fanconi anemia is included in this overview because of macrocytosis and/or anemia detected in the majority of the patients before they develop bone marrow failure.

[Hemoglobinopathies].

This article summarize molecular-genetic basis of hemoglobinopathies, their classification and phenotypic manifestations. The description of individual subgroups is supplemented with a case reports of patients diagnosed in the Czech population. This paper provides an overview of 14 types of α-thalassemic mutations, 34 β-thalassemic alleles, 4 δβ-thalassemic alleles and 22 hemoglobin variants identified in the Czech population in 876 persons from 579 families.

Hepcidin in newly diagnosed inflammatory bowel disease in children.

Aim: Hepcidin is a central regulator of iron homeostasis. Its production is also influenced by systemic inflammation. The aims of this study were to compare hepcidin levels in paediatric patients newly diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) and to determine the association of hepcidin levels with laboratory and clinical parameters of inflammatory bowel disease (IBD) activity.

Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study.

An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment for 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia that required transfusions, hyperbilirubinemia, hydrops, and prematurity.

Two novel mutations (p.(Ser160Pro) and p.(Arg472Cys)) causing glucose-6-phosphate isomerase deficiency are associated with erythroid dysplasia and inappropriately suppressed hepcidin.

Glucose-6-phosphate isomerase (GPI) deficiency, a genetic disorder responsible for chronic nonspherocytic hemolytic anemia, is the second most common red blood cell glycolytic enzymopathy. We report three patients from two unrelated families of Czech and Slovak origin with macrocytic hemolytic anemia due to GPI deficiency. The first patient had 15% of residual GPI activity resulting from two new heterozygous missense mutations c.

Recommendations regarding splenectomy in hereditary hemolytic anemias.

Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications.

Cooperation of germ line JAK2 mutations E846D and R1063H in hereditary erythrocytosis with megakaryocytic atypia.

The role of somatic JAK2 mutations in clonal myeloproliferative neoplasms (MPNs) is well established. Recently, germ line JAK2 mutations were associated with polyclonal hereditary thrombocytosis and triple-negative MPNs. We studied a patient who inherited 2 heterozygous JAK2 mutations, E846D from the mother and R1063H from the father, and exhibited erythrocytosis and megakaryocytic atypia but normal platelet number.