Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014848 (achalasia)
 2,804 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with chagasic achalasia (megaesophagus) are liable to have an additional 1.7-20% possibility of developing esophageal squamous cell carcinoma (ESCC). We applied a fluorescence in situ hybridization technique in 20 such patients and found aneuploidies of chromosomes 7, 11, and 17 in 60% (12 of 20 specimens) and deletion of the TP53 gene in 54.5% (6 of 11 specimens; it was only possible to obtain data by FISH technique from 11 of the 20 achalasia patients). The main aneuploidies detected were chromosome 7 monosomy or trisomy (35%) in mid-third megaesophagus cases, and chromosome 17 monosomy or trisomy (25%) in distal-third cases. TP53 gene deletion was more frequent in mid-third (62.5%) than in distal-third megaesophagus cases (40%). In chagasic megaesophagus, no amplification of the cyclin D1 gene (CCND1) was observed. Comparing chagasic megaesophagus to ESCC, we found a higher frequency of aneuploidies in all 10 tumors. The main alterations were trisomy or tetrasomy of chromosomes 17 (90%), 11 (70%), and 7 (70%). Amplification of CCND1 was evidenced as a cluster in 70% of the tumors (22-99% of nuclei), while TP53 gene deletion occurred in 100%. To our knowledge, this is the first cytogenetic analysis of chagasic megaesophagus to show that aneuploidies of chromosomes 7, 11, and 17, and TP53 gene deletion might be related to increased risk for malignancy.
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PMID:Cytogenetic alterations in chagasic achalasia compared to esophageal carcinoma. 1510 78

Down syndrome (DS) is the most common chromosomal abnormality occurring in humans. Up to 77% of DS children have associated gastrointestinal (GI) abnormalities, which may be structural or functional in nature. Functional disturbances may, in turn, affect the outcome of corrective surgical procedures, prompting to caution. It is becoming clear that the processes affecting the enteric nervous system (ENS) in DS not only affect the micro-anatomy but also nerve function, and there is some histological evidence of ENS variations in both human and DS animal models. This suggests that developmental disorders of the ENS are probably fundamental to the functional GI disturbances encountered in patients with DS. The anomalous brain development, function and resulting intellectual impairment associated with DS appears to result from the genetic imbalance created by the trisomy of chromosome 21. The possible links between the brain, GI and ENS involvement are not as yet entirely clear. Neurotropic factors affecting brain development during embryogenesis are probably interlinked with ENS development, but the precise mechanism of how this occurs has yet to be established. This study explores what is known about the ENS dysfunction in DS and reviews the possible importance of chromosome 21 located and other genes in its etiology. Functional motor disturbances of the esophagus and colon are not uncommon and may be congenital or acquired in nature. The most prominent of these include esophageal dysmotility syndromes (e.g. achalasia, gastroesophageal reflux, dysphagia) as well as a higher incidence of chronic constipation and Hirschsprung's disease (HSCR) (2-15%) occurring in association with DS. Chromosome 21 itself is thought to be the site of a modifier gene for HSCR. Recently identified candidate genetic mechanisms provide unique insights into the genetic background of the neurological and cognitive disorders associated with DS. Although the role of the triplicated chromosome 21 and genetic dosage remain important, the additional role of other chromosome 21 genes in the etiology of ENS developmental anomalies remains undetermined and requires ongoing research.
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PMID:Down syndrome and the enteric nervous system. 1863 23