Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0700208 (scoliosis)
 8,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two brothers presented with unusual facial features, microcephaly, developmental delay, and severe postnatal growth retardation. They both developed eczema in infancy and have had recurrent infections. Additional physical findings in both boys included hypogonadism, flexion contractures, hypoplastic patellae, and scoliosis. Their facial similarity was striking with sloping foreheads, beaked noses, large, protruding ears, and micrognathia. Low levels of serum gammaglobulins and defective chemotaxis were present in both boys in infancy. The hypogammaglobulinaemia was transient and improved, reaching normal levels by 3 1/2 years and 15 months, respectively. Defective chemotaxis and recurrent infections have persisted to the present. Both parents were normal. The mode of inheritance was not clear, as both X linked and autosomal recessive patterns were possible. Although patients with congenital malformations who also had immunodeficiency have previously been reported, immune system abnormalities, especially those of a transient nature, may frequently go unrecognised.
 ...
PMID:Microcephaly, short stature, and developmental delay associated with a chemotactic defect and transient hypogammaglobulinaemia in two brothers. 374 38

Concerns about the transmission of the human immunodeficiency virus (HIV) have driven the evolution of surgical transfusion practices including the use of preoperative erythropoietin (rhEPO). Although there is significant experience documenting the efficacy of preoperative rhEPO in reducing transfusion requirements for adult patients, there is little experience in the pediatric population. With 178 pediatric patients who underwent surgery for spinal deformity, a retrospective cohort study was performed using patient charts, administrative records, and blood bank computer data. Of these patients, 44% received erythropoietin and 55% did not. From the entire population, 17.5% were in the rhEPO treatment group that received homologous blood transfusion compared with 30.6% in the untreated group (p < 0.05). Among the children with idiopathic scoliosis, this effect was more pronounced, with 3.9% of rhEPO patients receiving blood transfusion compared with 23.5% of nontreated patients (p = 0.006). Additionally, rhEPO treatment was associated with a significantly decreased length of stay only for patients in the idiopathic group (9.3 vs. 6.7, p = 0.02). Use of preoperative erythropoietin in pediatric patients undergoing scoliosis surgery resulted in higher preoperative hematocrit levels. Significantly lower rates of transfusion were noted only in the idiopathic group, however. Although there is a possibility of erythropoietin "resistance" in the neuromuscular and congenital patients, alternative explanations for the lack of effect on transfusion rates may include underdosing and biases existent in this nonrandomized retrospective study.
 ...
PMID:The effectiveness of preoperative erythropoietin in averting allogenic blood transfusion among children undergoing scoliosis surgery. 970 70

Hyperimmunoglobulin-E syndrome is one of the primary immunodeficiency with the manifestations of recurrent infections especially with Staphylococcus aureus, characteristic facies, hyperextensibility of joints, multiple bone fractures, scoliosis, and delayed shedding of the primary teeth. It is a multisystem disease of autosomal dominant inheritance. Recently, a new type of hyper-IgE syndrome with autosomal recessive inheritance was identified. Although Th1/Th2 imbalance has been suspected to be a cause of this diesease, it is not clarified yet.
 ...
PMID:[Hyper-IgE syndrome]. 1567 88

Hyper IgE recurrent infection syndrome (HIES, or Job's syndrome) is a primary immunodeficiency characterized by recurrent skin and lung infections, eczema, elevated serum immunoglobulin E (IgE) levels, and various connective tissue and skeletal system abnormalities including characteristic facies, scoliosis, joint hyperextensibility, retained primary dentition, craniosynostosis, osteopenia, and pathologic fractures. We have identified two patients with aneurysmal coronary artery disease. One was a forty-three-year-old man with HIES and coronary artery aneurysms and ectasia identified on cardiac catheterization following myocardial infarction. The other was a 48-year-old man with coronary artery ectasia-aneurysm identified after cardiac catheterization for evaluation of chest pain. Although connective tissue abnormalities are common in HIES, this is the first report of coronary artery aneurysms in HIES. Further studies are necessary to determine the incidence, pathogenesis, and optimal therapy of these arterial abnormalities in HIES.
 ...
PMID:Coronary artery aneurysms in patients with hyper IgE recurrent infection syndrome. 1709 78

Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by atopic manifestations and susceptibility to infections with extracellular bacteria and fungi, which frequently occur in the skin and lung. Atopic manifestations in HIES include extremely high serum IgE levels, eczema and eosinophilia. Most of the extracellular bacterial infections are associated with disproportionally milder inflammation than normal, which was originally described as having a 'cold abscess'. Non-immunological abnormalities are also observed in most patients with HIES, including a distinctive facial appearance, scoliosis, hyper-extensive joints and retained primary teeth. Recent studies have demonstrated that hypomorphic mutations in signal transducer and activator of transcription 3 result in the classical multisystem form of HIES, whereas a null mutation in tyrosine kinase 2 causes the autosomal recessive form of HIES that is associated with viral and mycobacterial infections. Analyses of cytokine responses in both types of HIES have revealed defects in signal transduction for multiple cytokines including IL-6 and IL-23, leading to impaired T(h)17 function. These results suggest that the defect in multiple cytokine signals is the molecular basis of the immunological and non-immunological abnormalities in HIES and that the susceptibility to infections with extracellular bacteria and fungi in HIES might be associated with the defect in T(h)17 cell differentiation.
 ...
PMID:Defects in Jak-STAT-mediated cytokine signals cause hyper-IgE syndrome: lessons from a primary immunodeficiency. 1908 64

Autosomal dominant Hyper-IgE syndrome (AD-HIES) is a rare primary immunodeficiency characterized by eczema, recurrent skin and lung infections, elevated serum IgE, and various connective tissue, skeletal, and vascular abnormalities. Mutations in signal transducer and activator of transcription 3 (STAT3) have recently been found to account for most cases; however, the pathogenesis of the varied features remains poorly defined. A distinct syndrome, known as autosomal recessive HIES (AR-HIES) manifests as severe eczema, recurrent bacterial and viral skin infections, and sinopulmonary infections. As opposed to STAT3 deficient HIES, AR-HIES lacks the connective tissue and skeletal manifestations but has an increase in neurologic abnormalities. In this review, we discuss the clinical presentations, genetic etiologies, and immunologic abnormalities of these two syndromes. In addition, we discuss animal models of STAT3 deficiency that provide insight into the pathogenesis of HIES. Further understanding of how STAT3 results in the diverse manifestations of HIES will allow us to develop more specific therapies for HIES as well as for many of the manifestations, such as scoliosis, recurrent staphylococcal infections, and eczema, which are common in the general population.
 ...
PMID:Clinical manifestations, etiology, and pathogenesis of the hyper-IgE syndromes. 1919 May 25

Hyper IgE syndrome (HIES) is a rare primary immunodeficiency characterized by the triad of elevated IgE and eosinophilia, eczema, and recurrent skin and pulmonary infections. The autosomal dominant (AD) form of HIES results from mutations in STAT3 and is characterized by disordered inflammation, connective tissue, and skeletal abnormalities. Tissue-specific STAT3 deficiency in animals, cytokine and transcriptional array data, and careful clinical phenotyping have explained some of the pathophysiology of the immunologic and non-immunologic abnormalities of AD-HIES. In depth study of the role of STAT3 mutations in specific aspects of HIES may lead to better understanding and new approaches to treatment of conditions intrinsic to HIES that are common in the general population, such as staphylococcal infections, scoliosis, osteoporosis, bronchiectasis, and arterial aneurysms. As the genotypes of STAT3 deficiency are further characterized, genotype-phenotype correlations may emerge that will be informative regarding specific molecular interactions. Autosomal recessive forms of hyper IgE (AR-HIES) have also been reported. A single case of homozygous deficiency of the signal protein Tyk2 has been reported as well as a recessive syndrome with some features overlapping AD-HIES, but for which the genetic etiology is unknown. Better understanding of the pathophysiology and mechanisms of dominant and recessive hyper IgE syndromes will shed light on somatic and immune biology and may improve quality of life and survival for HIES patients.
 ...
PMID:Pathogenesis of hyper IgE syndrome. 1945 85

Hyper-IgE syndrome (HIES) is a complex primary immunodeficiency characterized by atopic dermatitis associated with extremely high serum IgE levels and susceptibility to infections with extracellular bacteria. Nonimmunological abnormalities, including a distinctive facial appearance, fracture following minor trauma, scoliosis, hyperextensive joints, and the retention of deciduous teeth are also observed in most patients. Recent studies have demonstrated that dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3) gene result in the classical multisystem form of HIES, whereas a null mutation in the tyrosine kinase 2 (TYK2) gene causes an autosomal recessive HIES associated with viral and mycobacterial infections. In both patients, signal transduction for multiple cytokines, including IL-6 and IL-23, was defective, resulting in impaired T(H)17 function. These findings suggest that the defect in cytokine signaling constitutes the molecular basis for the immunological and nonimmunological abnormalities observed in HIES.
 ...
PMID:Hyper-IgE syndrome. 1971 92

The hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterized by a highly elevated serum IgE, recurrent staphylococcal skin abscesses and cyst-forming pneumonia. Non-immunological abnormalities, including a distinctive facial appearance, hyperextensive joints, scoliosis, fracture following minor trauma, and the retention of primary teeth are also observed in many patients. Recently, it was shown that heterozygous mutations in signal transducer and activator of transcription 3 (STAT3), can cause autosomal-dominant HIES. Here we identify and characterize a novel mutation in the DNA-binding domain of STAT3 in a patient with hyper-IgE syndrome. Sequence analysis revealed a de novo heterozygous transition of a G-to-A, causing a substitution of a glycine residue for an aspartic acid in the translated sequence (G342D). The patient has normal levels of STAT3, which is able to translocate to the nucleus upon IL-6 stimulation. However, enzyme-linked DNA-protein interaction analysis showed that the G342D mutation affects the binding ability of STAT3 to target DNA sequences. In addition, as shown by qRT-PCR, the mutation abrogates the STAT3-dependent transcription of the retinoid-related orphan receptor gammat (ROR gammat) gene, an indispensable transcription factor for the commitment of naive CD4+ T cells to the Th17 lineage. These data suggest that the novel G342D mutation affects the binding of STAT3 on DNA and the STAT3-dependent expression of ROR gammat mRNA, leading to the HIES phenotype.
 ...
PMID:A novel mutation in the signal transducer and activator of transcription 3 (STAT3) gene, in hyper-IgE syndrome. 2014 60

Hyperimmunoglobulin-E syndrome (HIES) is one of the primary immunodeficiency with the manifestations of recurrent infections especially with Staphylococcus aureus, characteristic facies, hyperextensibility of joints, multiple bone fractures, scoliosis, and delayed shedding of the primary teeth. It is a multisystem disease of autosomal dominant or recessive inheritance. Recently, the genetic causes of HIES (STAT3, TYK2, and DOCK8) were clarified.
 ...
PMID:[Recent advances in the pathogenesis of hyper IgE syndrome]. 2019 May 5


1 2 Next >>