Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021843 (bowel obstruction)
 9,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hirschsprung disease (HSCR) is a congenital disorder characterised by intestinal obstruction due to an absence of intramural ganglia along variable lengths of the intestine. RET is the major gene involved in HSCR. Mutations in the GDNF gene, and encoding one of the RET ligands, either alone or in combination with RET mutations, can also cause HSCR, as can mutations in four other genes (EDN3, EDNRB, ECE1, and SOX10). The rare mutations in the latter four genes, however, are more or less restricted to HSCR associated with specific phenotypes. We have developed a novel comprehensive mutation detection system to analyse all but three amplicons of the RET and GDNF genes, based on denaturing gradient gel electrophoresis. We make use of two urea-formamide gradients on top of each other, allowing mutation detection over a broad range of melting temperatures. For the three remaining (GC-rich) PCR fragments we use a combination of DGGE and constant denaturing gel electrophoresis (CDGE). These two dual gel systems substantially facilitate mutation scanning of RET and GDNF, and may also serve as a model to develop mutation detection systems for other disease genes. In a screening of 95 HSCR patients, RET mutations were found in nine out of 17 familial cases (53%), all containing long segment HSCR. In 11 of 78 sporadic cases (14%), none had long segment HSCR. Only one GDNF mutation was found, in a sporadic case.
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PMID:RET and GDNF gene scanning in Hirschsprung patients using two dual denaturing gel systems. 1079 Feb 3

Hirschsprung disease (HSCR), the most common hereditary cause of intestinal obstruction, shows considerable variation and complex inheritance. Coding sequence mutations in RET, GDNF, EDNRB, EDN3 and SOX10 lead to long-segment (L-HSCR) and syndromic HSCR but fail to explain the transmission of the much more common short-segment form (S-HSCR). We conducted a genome scan in families with S-HSCR and identified susceptibility loci at 3p21, 10q11 and 19q12 that seem to be necessary and sufficient to explain recurrence risk and population incidence. The gene at 10q11 is probably RET, supporting its crucial role in all forms of HSCR; however, coding sequence mutations are present in only 40% of linked families, suggesting the importance of noncoding variation. Here we show oligogenic inheritance of S-HSCR, the 3p21 and 19q12 loci as RET-dependent modifiers, and a parent-of-origin effect at RET. This study demonstrates by a complete genetic dissection why the inheritance pattern of S-HSCR is nonmendelian.
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PMID:Segregation at three loci explains familial and population risk in Hirschsprung disease. 1195 48

Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a common hereditary disorder causing intestinal obstruction, thereby showing considerable phenotypic variation in conjunction with complex inheritance. Moreover, phenotypic assessment of the disease has been complicated since a subset of the observed mutations is also associated with several additional syndromic anomalies. Coding sequence mutations in e.g. RET, GDNF, EDNRB, EDN3, and SOX10 lead to long-segment (L-HSCR) as well as syndromic HSCR but fail to explain the transmission of the much more common short-segment form (S-HSCR). Furthermore, mutations in the RET gene are responsible for approximately half of the familial and some sporadic cases, strongly suggesting, on the one hand, the importance of non-coding variations and, on the other hand, that additional genes involved in the development of the enteric nervous system still await their discovery. For almost all of the identified HSCR genes incomplete penetrance of the HSCR phenotype has been reported, probably due to modifier loci. Therefore, HSCR has become a model for a complex oligo-/polygenic disorder in which the relationship between different genes creating a non-mendelian inheritance pattern still remains to be elucidated.
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PMID:Hirschsprung, RET-SOX and beyond: the challenge of examining non-mendelian traits (Review). 1223 80

Hirschsprung's disease is a birth defect that affects about one out of 5000 newborns. It is one of the most common causes of intestinal obstruction at the babies. The objectives of this study are to evaluate the characteristics of Hirschsprung's disease in Dobrogea area, test of genetic markers in families and single cases, estimate the value of the test in the diagnosis and for evolution. We made a case-control study for the period 1995-2006 and analyzed 21 cases of Hirschsprung's disease, which were treated in the Emergency County Hospital, Constanta. The diagnostic methods comprised clinical and paraclinical examination. The chromosomal markers used in the study are represented by four categories of chromosome abnormalities: Trisomy 21, Del 10q, Del 13q, Del 17q. The molecular markers investigated by us are represented by: RET, EDNRB and EDN3. We made the correlation of genetic markers with the anatomopathological and histopathological forms, by measuring the level of association, expressed by the calculated relative risk (OR) and using the correlation index f. Based on data obtained from the group investigated, we found that the indices of association and correlation are consistently higher compared to DNA-markers with chromosomal markers, both for anatomopathological forms as well as histopathological. We noticed that no chromosomes markers were recorded with indices of correlation with negative values, which means that these chromosomal abnormalities are involved with a particular quota to the release of disease.
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PMID:The correlation of genetic markers with anatomoclinical and histopathological forms in Hirschsprung's disease. 2049 44