Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
LGC Clinical Diagnostics

Download Mobile App




Suite of Risk Variants Revealed in Hirschsprung's Disease

By LabMedica International staff writers
Posted on 23 Apr 2019
Hirschsprung’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, often appearing in combination with other symptoms in a manner that may reflect specific syndromes.

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. Genetic factors that contribute to a highly heritable developmental condition of Hirschsprung's disease include a complex suite of risk variants, ranging from common polymorphisms in non-coding elements to rarer coding variants and copy number variants (CNVs).

Scientists at several institutions collaborated with those at Johns Hopkins University (Baltimore, MD, USA) and 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 CNVs, and karyotype variants in probands were considered to be pathogenic when they were significantly associated with Hirschsprung’s disease or another neurodevelopmental disorder. These were compared with 627 unaffected controls, including 404 participants in the 1000 Genomes Project 223 so-called "pseudo-controls," parental chromosomes that were not transmitted to the affected children.

The team reported that the 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. Rare coding variants in 24 genes that play roles in enteric neural-crest cell fate, seven 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). Large CNVs, which were present in fewer patients, 11.4%, as compared with 0.2% of controls, conferred the highest risk (odds ratio, 63.07). 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).

The authors concluded that among the patients in their 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. The study was published on April 11, 2019, in the New England Journal of Medicine.

Related Links:
Johns Hopkins University


Gold Member
Troponin T QC
Troponin T Quality Control
Verification Panels for Assay Development & QC
Seroconversion Panels
New
Aspergillus Test
REALQUALITY Aspergillus
New
Centrifuge
Hematocrit Centrifuge 7511M4
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








Channels

Clinical Chemistry

view channel
Image: The tiny clay-based materials can be customized for a range of medical applications (Photo courtesy of Angira Roy and Sam O’Keefe)

‘Brilliantly Luminous’ Nanoscale Chemical Tool to Improve Disease Detection

Thousands of commercially available glowing molecules known as fluorophores are commonly used in medical imaging, disease detection, biomarker tagging, and chemical analysis. They are also integral in... Read more

Immunology

view channel
Image: The cancer stem cell test can accurately choose more effective treatments (Photo courtesy of University of Cincinnati)

Stem Cell Test Predicts Treatment Outcome for Patients with Platinum-Resistant Ovarian Cancer

Epithelial ovarian cancer frequently responds to chemotherapy initially, but eventually, the tumor develops resistance to the therapy, leading to regrowth. This resistance is partially due to the activation... Read more

Microbiology

view channel
Image: The lab-in-tube assay could improve TB diagnoses in rural or resource-limited areas (Photo courtesy of Kenny Lass/Tulane University)

Handheld Device Delivers Low-Cost TB Results in Less Than One Hour

Tuberculosis (TB) remains the deadliest infectious disease globally, affecting an estimated 10 million people annually. In 2021, about 4.2 million TB cases went undiagnosed or unreported, mainly due to... Read more

Pathology

view channel
Image: The ready-to-use DUB enzyme assay kits accelerate routine DUB activity assays without compromising data quality (Photo courtesy of Adobe Stock)

Sensitive and Specific DUB Enzyme Assay Kits Require Minimal Setup Without Substrate Preparation

Ubiquitination and deubiquitination are two important physiological processes in the ubiquitin-proteasome system, responsible for protein degradation in cells. Deubiquitinating (DUB) enzymes contain around... Read more

Technology

view channel
Image: The HIV-1 self-testing chip will be capable of selectively detecting HIV in whole blood samples (Photo courtesy of Shutterstock)

Disposable Microchip Technology Could Selectively Detect HIV in Whole Blood Samples

As of the end of 2023, approximately 40 million people globally were living with HIV, and around 630,000 individuals died from AIDS-related illnesses that same year. Despite a substantial decline in deaths... Read more

Industry

view channel
Image: The collaboration aims to leverage Oxford Nanopore\'s sequencing platform and Cepheid\'s GeneXpert system to advance the field of sequencing for infectious diseases (Photo courtesy of Cepheid)

Cepheid and Oxford Nanopore Technologies Partner on Advancing Automated Sequencing-Based Solutions

Cepheid (Sunnyvale, CA, USA), a leading molecular diagnostics company, and Oxford Nanopore Technologies (Oxford, UK), the company behind a new generation of sequencing-based molecular analysis technologies,... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.