Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in with BA risk (odds ratio (OR) = 1.
View Article and Find Full Text PDFThe ankyrin repeat and sterile alpha motif domain containing 6 (ANKS6) gene, encoding an inversin compartment protein of the primary cilium, was recently reported as a pathogenic gene of nephronophthisis (MIM PS256100). Extrarenal manifestations are frequently observed in this disease, however, potential genotype-phenotype correlations and the underlying mechanisms remain poorly understood. Here we described an infant with kidney failure, hepatobiliary abnormalities, and heart disease, in whom whole exome sequencing identified compound heterozygous variants in ANKS6, including a novel nonsense variant p.
View Article and Find Full Text PDFBiliary atresia (BA) is a destructive, obliterative cholangiopathy characterized by progressive fibro-inflammatory disorder and obliteration of intra- and extrahepatic bile ducts. The () gene mutations have been found in some isolated BA cases. We aim to explore the association of common variants in with isolated BA risk in the Chinese Han population.
View Article and Find Full Text PDFBackground & Aims: Regenerating gene family member 4 (REG4) is a novel marker for enteroendocrine cells and is selectively expressed in specialised enteroendocrine cells of the small intestine. However, the exact roles of REG4 are largely unknown. In this study we investigate the effects of REG4 on the development of dietary fat-dependent liver steatosis and the mechanisms involved.
View Article and Find Full Text PDFInsights into the role of microRNAs (miRNAs) in disease pathogenesis have made them attractive therapeutic targets, and numerous miRNAs have been functionally linked to Hirschsprung disease (HSCR), a life-threatening genetic disorder due to defective migration, proliferation, and colonization of enteric neural crest cells (ENCCs) in the gut. Recent studies have demonstrated that miR-424 strongly inhibits migration in a variety of cell types and its potential target is essential for neural crest cell development. We therefore sought to interrogate how miR-424 and contribute to the pathogenesis of HSCR.
View Article and Find Full Text PDFThe leiomodin1 (LMOD1) gene, encoding a potent actin nucleator, was recently reported as a potential pathogenic gene of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS, OMIM 619362). However, only a single patient has been reported to have LMOD1 mutations, and the underlying pathogenic mechanism remains unknown. Here, we described a male infant with LMOD1 mutations presenting typical symptoms of pediatric intestinal pseudo-obstruction (PIPO) but without megacystis and microcolon.
View Article and Find Full Text PDFHirschsprung disease (HSCR) has a higher incidence in children with Down syndrome (DS), which makes trisomy 21 a predisposing factor to HSCR. and are close together on the HSCR-associated critical region of chromosome 21. Common variants of and rare variants of were implicated to be associated with sporadic HSCR.
View Article and Find Full Text PDFHirschsprung's disease (HSCR) is a rare genetically heterogeneous congenital disorder. A recent study based on whole genome sequencing demonstrated that common variants at four novel loci, which contained two intronic variants on and , and intergenic variants located between and at 3p24.1, and between and at 10q11.
View Article and Find Full Text PDFBackground: Hirschsprung disease (HSCR) is a neurodevelopmental disorder with a strong genetic component. Common variants of NRG1 contributed to HSCR risk in Asians, and rare variants of ERBB2 and ITGB4 were found to be associated with HSCR. ERBB2 and ITGB4 are partners of Nrg1/ErbB pathway, which is important in HSCR pathogenesis.
View Article and Find Full Text PDFBackground: Hirschsprung's disease (HSCR) is the most common congenital cause of intestinal obstruction in children. Sotos syndrome (SoS) is an overgrowth disorder with constipation and sometimes accompanied by HSCR. NSD1 gene mutation is the main cause of SoS.
View Article and Find Full Text PDFBiliary atresia (BA) is an idiopathic neonatal cholestatic disease. Recent genome-wide association study (GWAS) revealed that common variation of , , , and gene was associated with BA susceptibility. We aimed to evaluate the association of these genes with BA in Chinese population.
View Article and Find Full Text PDFHirschsprung disease (HSCR), the most common enteric neuropathy, stands as a model for complex genetic disorders. It has recently been demonstrated that both and map to the -dependent HSCR susceptibility loci. We therefore sought to explore whether genetic variants within , and , and their genetic interaction networks are associated with HSCR.
View Article and Find Full Text PDFBackground: Hirschsprung disease (HSCR) is a life-threatening congenital disorder in which the enteric nervous system is completely missing from the distal gut. Recent studies have shown that miR-4516 markedly inhibits cell migration, and as one of its potential targets, functions as a modifier for developing HSCR. We thus aimed to evaluate the role of miR-4516 and in HSCR and how they contribute to the pathogenesis of HSCR.
View Article and Find Full Text PDFIntestinal villus atrophy is a major complication of total parenteral nutrition (TPN). Our previous study revealed that TPN-induced villus atrophy is accompanied by elevated expression of CUGBP, Elav-like family member 1 (CELF1); however, its mechanism of action has not been fully understood. Herein, we report a pivotal role of CELF1/p53 axis, which induces a sustained antiproliferative signal, leading to suppressed proliferation of intestinal epithelial cells (IECs).
View Article and Find Full Text PDFHirschsprung disease (HSCR) is a severe multifactorial genetic disorder. Microarray studies indicated GAL, GAP43 and NRSN1 might contribute to the altered risk in HSCR. Thus, we focused on genetic variations in GAL, GAP43 and NRSN1, and the gene-gene interactions involved in HSCR susceptibility.
View Article and Find Full Text PDFBackground And Aims: Elevated intestinal permeability of lipopolysaccharide (LPS) is a major complication for patients with parenteral nutrition (PN), but the pathogenesis is poorly understood. Intestinal P-glycoprotein (P-gp) is one of the efflux transporters that contribute to restricting the permeability of lipopolysaccharide via transcellular route. P-gp expression may be regulated by PN ingredients, and thus this study sought to investigate the effect of PN on the expression of P-gp and to elucidate the underlying mechanism in vitro.
View Article and Find Full Text PDFThe effectiveness and stability of epithelial barrier depend on apical junctional complexes, which consist of tight junctions (TJs) and adherens junctions (AJs). E-cadherin is the primary component of AJs, and it is essential for maintenance of cell-to-cell interactions and regulates the epithelial barrier. However, the exact mechanism underlying E-cadherin expression, particularly at the posttranscriptional level, remains largely unknown.
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