Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital heart disease is a significant cause of morbidity and mortality in humans, and gene mutations that underlie some of these anomalies are now being described. The NKX2.5 gene, which encodes a homeobox transcription factor, was initially discovered in mice through its similarity to the tinman gene of the fruitfly Drosophila. Tinman is required for formation of the dorsal pulsatile vessel or 'heart' of the fly. Tinman and NKX2.5 share structural and functional features, and in mice the gene is required for normal cardiac looping and differentiation of chamber myocardium. Humans with heterozygous mutations in the NKX2.5 gene generally have a disorder involving progressive atrio-ventricular conduction block and atrial septal defect, although sometimes other abnormalities including tetralogy of Fallot. The TBX5 gene, which encodes another cardiac transcription factor that collaborates with NKX2.5, is also an important cardiac disease gene, with heterozygous mutations responsible for Holt-Oram (hand/heart) syndrome. These contributions to human pathology underscore the relevance of studying biological phenomena in lower organisms, and examination of other genes acting in this and associated pathways will expand our knowledge of congenital abnormalities and disease predisposition, and improve genetic counseling.
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PMID:Developmental paradigms in heart disease: insights from tinman. 1217 84

Congenital heart disease (CHD), one of the causes of childhood morbidity and mortality, is mainly triggered by a combination of environmental and genetic factors. Several susceptible genes, such as NKX2-5, GATA4 and TBX5, have been reported as closely related to heart and vessel development. CHD subtypes are classified into diverse clinical phenotypes, such as atrial septal defects (ASD), ventricular septal defects (VSD), tetralogy of Fallot (TOF), and Holt-Oram syndrome (HOS). Here, we summarize the associations of the genetic variants in these three genes with CHD subtypes. CHD-associated variants of NKX2-5 locate mainly in the tinman domain and the homeodomain. Mutations in the homeodomain are correlated with ASD and atrioventricular (AV) block subtypes. VSD-associated variants of GATA4 are mainly at its terminal ends. Variants of TBX5 gene are primarily in exons 3, 4, 5 and 7 and highly associated with HOS subtype. Hence, the variant distribution of NKX2-5, GATA4 and TBX5 are tightly associated with particular CHD subtypes. Further structure-modelling analysis revealed that these mutated amino acid residuals maintain their DNA-binding ability and structural stability. Therefore structural features of these genes may be used to predict the high risk of CHD subtypes in infants.
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PMID:Congenital heart diseases and their association with the variant distribution features on susceptibility genes. 2742 23

Congenital heart disease (CHD) is the leading cause of infant death, affecting approximately 4-14 live births per 1,000. Although surgical techniques and interventions have improved significantly, a large number of infants still face poor clinical outcomes. MicroRNAs (miRs) are known to coordinately regulate cardiac development and stimulate pathological processes in the heart, including fibrosis or hypertrophy and impair angiogenesis. Dysregulation of these regulators could therefore contribute (I) to the initial development of CHD and (II) at least partially to the observed clinical outcomes of many CHD patients by stimulating the aforementioned pathways. Thus, miRs may exhibit great potential as therapeutic targets in regenerative medicine. In this review we provide an overview of miR function and elucidate their role in selected CHDs, including hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TOF), ventricular septal defects (VSDs) and Holt-Oram syndrome (HOS). We then bridge this knowledge to the potential usefulness of miRs and/or their targets in therapeutic strategies for regenerative purposes in CHDs.
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PMID:MicroRNAs: pleiotropic players in congenital heart disease and regeneration. 2844 69