Pathogenesis of Hirschsprung's disease and its variants: recent progress.

@article{Puri2004PathogenesisOH,
  title={Pathogenesis of Hirschsprung's disease and its variants: recent progress.},
  author={Prem Lata Puri and Toko Shinkai},
  journal={Seminars in pediatric surgery},
  year={2004},
  volume={13 1},
  pages={
          18-24
        }
}
The enteric nervous system (ENS) is a complex network of interconnected neurons within the wall of the intestine that controls intestinal motility, regulates mucosal secretion and blood flow, and also modulates sensation from the gut. The cells that form the ENS in mammals are derived primarily from vagal neural crest cells. During the past decade there has been an explosion of information about genes that control the development of neural crest. Molecular-genetic analysis has identified… 

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References

SHOWING 1-10 OF 122 REFERENCES
Hirschsprung's disease: a search for etiology.
Genetic aspects of Hirschsprung's disease.
Enteric Nervous System: Development and Developmental Disturbances—Part 1
  • D. Newgreen, H. Young
  • Biology
    Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
  • 2002
This review, which is presented in two parts, summarizes and synthesizes current views on the genetic, molecular, and cell biological underpinnings of the early embryonic phases of enteric nervous
Pathogenesis of Hirschsprung's disease.
TLDR
The RET proto-oncogene accounts for the highest proportion of both familial and sporadic cases, with a wide range of mutations scattered along its entire coding region, and microenvironmental factors also can play a role in the pathogenesis of aganglionosis.
Mutations of the RET proto-oncogene in Hirschsprung's disease
TLDR
No recombination was observed between the disease locus and the locus for the RET proto-oncogene, a protein tyrosine kinase gene expressed in the cells derived from the neural crest, and it is shown that the mutant genotypes segregate with the disease in HSCR families.
Enteric Nervous System: Development and Developmental Disturbances—Part 2
  • D. Newgreen, H. Young
  • Biology
    Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
  • 2002
This review, which is presented in two parts, summarizes and synthesizes current views on the genetic, molecular, and cell biological underpinnings of the early embryonic phases of enteric nervous
Genetics of Hirschsprung disease
TLDR
HSCR has become a model of a complex polygenic disorder in which the interplay of different genes is currently being elucidated, and for almost every HSCR gene, incomplete penetrance of the H SCR phenotype has been observed.
Abnormalities of the enteric nervous system in heterozygous endothelin B receptor deficient (spotting lethal) rats resembling intestinal neuronal dysplasia
TLDR
The present findings support the concept of IND based on clearly defined morphological criteria suggesting a genetic link, and thus may provide a model for human IND.
From neural crest to bowel: development of the enteric nervous system.
TLDR
Although the factors that are responsible for the development of the unique properties of the ENS remain unknown, progress made in understanding enteric neuronal development has recently accelerated and the application of new techniques and recently developed probes suggest that the accelerated pace of discovery can be expected to continue.
Endothelin-3 Gene Mutations in Isolated and Syndromic Hirschsprung Disease
TLDR
The present data give further support to the role of the endothelin-signaling pathway in the development of neural crest-derived enteric neurons and suggest the possibility that either recessive or weakly penetrant dominant alleles could occur at the EDN3 locus, depending on the nature of the mutation.
...
...