Hirschsprung disease (HSCR), a multifactorial disorder of enteric nervous system (ENS) development, is associated with at least 24 genes and seven chromosomal loci, with RET and EDNRB as its major genes.
Our findings suggested that autosomal recessive mutation in EDNRB may underlie a part of WS1 with the current diagnostic criteria, and supported that Hirschsprung's disease is a multifactorial genetic disease which requires additional factors.
In the present study, we demonstrated that SEMA3A expression is increased in the EDNRB-/- HD model on P2, suggesting that SEMA3A may interfere with ENCC migration, resulting in an absence of enteric neurons.
The clinical association between Trisomy 21 (Down syndrome) and aganglionosis (Hirschsprung disease; DS-HSCR) is well-established, being of the order of 5% and remains the most common congenital association with Hirschsprung disease.
Future studies investigating the disease-associated mutations in the already identified HSCR genes should provide insights into the genetic basis of HSCR in twins.
Interestingly, homozygous (and very rare heterozygous) EDNRB mutations are already described in type IV WS (i.e., in association with Hirschsprung disease [HD]) and heterozygous mutations in isolated HD.
HSCR (aganglionic megacolon) is a frequent diagnostic and clinical challenge in perinatology and pediatric surgery, and a major cause of neonatal intestinal obstruction.
We report a novel non-sense EDNRB gene mutation in a girl with HSCR and her mother and grandmother with HSCR and MS. We propose that this EDNRB gene mutation plays a role in the etiology of HSCR and also makes the subjects susceptible to MS.
To explore a potential methodology for treating aganglionic megacolon, neural stem cells (NSCs) expressing engineered endothelin receptor type B (EDNRB) and glial cell-derived neurotrophic factor (GDNF) genes were transplanted into the aganglionic megacolon mice.
Here, we present the extension of a previous study of a Spanish series of HSCR trios to an international cohort of 162 HSCR trios to validate the generality of the underlying functional basis of the Hirschsprung's disease mechanisms previously found.
The genetics of Hirschsprung's disease are highly complex with the majority of known genetic sites relating to the main susceptibility pathways (RET an EDNRB).
The aim of this study was to evaluate the implication of the EDN3 and EDNRB genes in a series of patients with Hirschsprung disease from Spain and determinate their mutational spectrum.
Hirschsprung's disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine.The RET gene is the major HSCR gene.
One hundred twenty patients with HSCR (including 18 kindreds) were screened for genetic variations of the 2 major susceptibility genes (RET and endothelin B receptor [EDNRB]) and compared with 60 control samples (20 per ethnic group).
Because HSCR is a multifactorial and multigene disorder, the higher mutation rate of 10% for short-segment HSCR suggests the important role that the EDNRB gene plays in the pathogenesis of short-segment HSCR in Taiwan.
All 8 exons and intron/exon boundaries of the EDNRB gene in 18 Korean patients with sporadic HSCR and 84 healthy individuals were screened using PCR amplification and direct sequencing.
Homozygous mutations of EDNRB in human have been reported to result in Waardenburg-Hirschsprung disease (WS4), while mutated heterozygotes manifested isolated Hirschsprung disease in lower penetrance.