Dataset Information

Specific serum microRNA profile in the molecular diagnosis of Hirschsprung's disease.

ABSTRACT: Hirschsprung's disease (HSCR), a congenital gastrointestinal disorder, is one of the most common causes of neonatal bowel obstruction. Without an early screening and diagnosis, some patients develop serious complications, such as toxic megacolon or acute enterocolitis. We sought to identify specific serum microRNAs (miRNAs) that can serve as novel early, non-invasive screening signature and then to test their specificity and sensitivity in diagnosing Hirschsprung's disease. We obtained serum samples from 95 HSCR cases and 104 matched controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array. The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR arranged in the training and a two-stage validation set. Additional double-blind testing was performed in 23 patients with clinically suspected HSCR to evaluate the diagnostic value and accuracy of the serum miRNA profile in predicting HSCR. Following a multi-stage evaluation approach, five miRNAs were significantly increased in HSCR cases compared with controls. The areas under the receiver operating characteristic (ROC) curve of this five-serum miRNA signature were 0.895, 0.893 and 0.925 in training set and two validation sets, respectively. The accuracy rate of the five-miRNA profile as HSCR signature was 82.6%, which, in the double-blind testing set, was markedly higher than that of contrast enema (70%), the most commonly used test performed to diagnose HSCR. Our results indicate that a five-serum miRNA signature may be linked to HSCR, representing a potential, novel, non-invasive diagnostic approach for early screening of HSCR.

SUBMITTER: Tang W

PROVIDER: S-EPMC4190904 | biostudies-other | 2014 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Specific serum microRNA profile in the molecular diagnosis of Hirschsprung's disease.

Tang Weibing W Li Hongxing H Tang Junwei J Wu Wei W Qin Jingjing J Lei Hao H Cai Peng P Huo Weiwei W Li Bo B Rehan Virender V Xu Xiaoqun X Geng Qiming Q Zhang Hongwei H Xia Yankai Y

Journal of cellular and molecular medicine 20140628 8

Hirschsprung's disease (HSCR), a congenital gastrointestinal disorder, is one of the most common causes of neonatal bowel obstruction. Without an early screening and diagnosis, some patients develop serious complications, such as toxic megacolon or acute enterocolitis. We sought to identify specific serum microRNAs (miRNAs) that can serve as novel early, non-invasive screening signature and then to test their specificity and sensitivity in diagnosing Hirschsprung's disease. We obtained serum sam ...[more]

PMID: 24974861

Similar Datasets

Project description:BackgroundHirschsprung's disease, or congenital aganglionosis, is a developmental disorder of the enteric nervous system and is the most common cause of intestinal obstruction in neonates and infants. The disease has more than 80% heritability, including significant associations with rare and common sequence variants in genes related to the enteric nervous system, as well as with monogenic and chromosomal syndromes.MethodsWe genotyped and exome-sequenced samples from 190 patients with Hirschsprung's disease to quantify the genetic burden in patients with this condition. DNA sequence variants, large copy-number variants, and karyotype variants in probands were considered to be pathogenic when they were significantly associated with Hirschsprung's disease or another neurodevelopmental disorder. Novel genes were confirmed by functional studies in the mouse and human embryonic gut and in zebrafish embryos.ResultsThe presence of five or more variants in four noncoding elements defined a widespread risk of Hirschsprung's disease (48.4% of patients and 17.1% of controls; odds ratio, 4.54; 95% confidence interval [CI], 3.19 to 6.46). Rare coding variants in 24 genes that play roles in enteric neural-crest cell fate, 7 of which were novel, were also common (34.7% of patients and 5.0% of controls) and conferred a much greater risk than noncoding variants (odds ratio, 10.02; 95% CI, 6.45 to 15.58). Large copy-number variants, which were present in fewer patients (11.4%, as compared with 0.2% of controls), conferred the highest risk (odds ratio, 63.07; 95% CI, 36.75 to 108.25). At least one identifiable genetic risk factor was found in 72.1% of the patients, and at least 48.4% of patients had a structural or regulatory deficiency in the gene encoding receptor tyrosine kinase (RET). For individual patients, the estimated risk of Hirschsprung's disease ranged from 5.33 cases per 100,000 live births (approximately 1 per 18,800) to 8.38 per 1000 live births (approximately 1 per 120).ConclusionsAmong the patients in our study, Hirschsprung's disease arose from common noncoding variants, rare coding variants, and copy-number variants affecting genes involved in enteric neural-crest cell fate that exacerbate the widespread genetic susceptibility associated with RET. For individual patients, the genotype-specific odds ratios varied by a factor of approximately 67, which provides a basis for risk stratification and genetic counseling. (Funded by the National Institutes of Health.).

Project description:Aim: Postoperative lower gastrointestinal bleeding in children with Hirschsprung's Disease (HSCR) is a non-specific symptom, which may be caused by various etiologies. Our current study aims to utilize colonoscopy to diagnose the causes of postoperative hematochezia and to analyze its feasibility, accuracy, and safety. Methods: Twenty-four patients with HSCR with postoperative lower gastrointestinal bleeding or occult blood in the stool were enrolled in this study. The postoperative onset duration, age at examination, accompanied anomalies were recorded. After bowel preparation, all patients underwent colonoscopy. According to visual findings, mucosal biopsy was performed, followed by pathological diagnosis. Further treatment was determined according to the visual findings and pathological diagnosis. All patients were followed up for 6 months including therapeutic outcomes and recurrence of symptoms. Results: The mean onset duration was (221.3 ± 216.8) days postoperatively (ranging from 25 to 768 days). The mean age at examination was (41.0 ± 29.4) months. There was no significant difference in the onset days among each group (all, p > 0.05). Based on visual and pathological findings, there were 11 cases of HSCR associated enterocolitis (HAEC), 4 cases of anastomotic leakage, 7 cases of anastomotic inflammation, 1 case of juvenile polyp, and 1 case of inflammatory pseudopolyp. Intraluminal saline irrigation, thrombin treatment or colorectal polyp electrocision was performed according to intraoperative diagnosis. Patients with HEAC and anastomotic inflammation underwent antibiotics therapy and colorectal irrigation. Patients with leakage underwent reoperation. The highest incidence of accompanied symptoms of diarrhea existed in HEAC group (p = 0.02) and fever in leakage group (p = 0.02), respectively. No perforation or aggravated bleeding occurs in any patients. All patients gained uneventful recovery during follow-up period. Conclusions: Colonoscopy is a safe, accurate and timely examination for HSCR patients with postoperative lower gastrointestinal bleeding. The visual findings and biopsy may provide accurate diagnosis and guide treatment for this subset of patients.

Dataset Information

Specific serum microRNA profile in the molecular diagnosis of Hirschsprung's disease.

Publications

Specific serum microRNA profile in the molecular diagnosis of Hirschsprung's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets