Mutations of the RET proto-oncogene in Hirschsprung's disease

  title={Mutations of the RET proto-oncogene in Hirschsprung's disease},
  author={Patrick Edery and Stanislas Lyonnet and Lois M. Mulligan and Anna Pelet and E Dow and Laurent Abel and Susan E. Holder and Claire Nihoul-F{\'e}k{\'e}t{\'e} and Bruce A. J. Ponder and Arnold Munnich},
HIRSCHSPRUNG'S disease (HSCR)1 is a common condition (1 in 5,000 live births) resulting in intestinal obstruction in neonates2 and megacolon in infants and adults3. This disease has been ascribed to the absence of autonomic ganglion cells, which are derived from the neural crest, in the terminal hindgut4. Segregation analyses have suggested incompletely penetrant dominant inheritance in familial HSCR5. Recently, a gene for HSCR has been mapped to chromosome 10q11.2 (refs 6, 7). No recombination… 

Molecular-genetic analysis of Hirschsprung's disease in South Africa

It is demonstrated that all the potential disease-related mutations identified in South African patients with sporadic HSCR occur in the RET gene.

Hirschsprung’s disease: genetic mutations in mice and men

The possible roles of RET and endothelin in the normal development of the enteric nervous system, and the significance of their mutated forms in the pathogenesis of familial aganglionosis are reviewed.

Mapping of a Hirschsprung's disease locus in 3p21

A five-marker haplotype, spanning a 118 kb gene-rich region, was found to be overtransmitted to affected offspring and encompasses three genes involved in neurological phenotypes, and could be used in follow-up studies to finally pinpoint this HSCR locus.

Novel RET mutations in Hirschsprung's disease patients from the diverse South African population

This study represents the first comprehensive genetic analysis of HSCR in the diverse South African population and identifies five novel mutations and one previously described mutation.

Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes and Hirschsprung disease

The observation that the major tissues affected in MEN 2 and Hirschsprung disease have a common origin in the embryonal neural crest, suggest that RET encodes a receptor for a developmental regulator involved in the genesis of a variety of neural crest derivatives, and in the organogenesis of the kidney.

Novel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's disease.

Observations indicate that dysfunction or loss of function of endothelin-B receptor may be involved in the aetiology of some isolated patients with HSCR.

Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease

S segregation analysis suggested an incompletely penetrant dominant inheritance in HSCR families with agan-glionosis extending beyond the sigmoid colon, and mutations of the gene encoding GDNF could either cause or modulate the H SCR phenotype in some cases.



Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A

This work has identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls, and found that 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of theRET extracellular and transmembrane domains.

A gene for Hirschsprung disease maps to the proximal long arm of chromosome 10

Hirschsprung disease is a frequent congenital disorder of unknown origin characterized by the absence of parasympathetic intrinsic ganglion cells of the hindgut, suggesting that a dominant gene for HSCR maps to 10q11.2, a region to which other neural crest defects have been mapped.

Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC.

Evidence is presented that sequence changes within the coding region of the RET proto-oncogene, a putative transmembrane tyrosine kinase, may be responsible for the development of neoplasia in these inherited disorders.

A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10

Linkage in a subset of five HSCR families to the pericentromeric region of chromosome 10 is identified, thereby proving monogenic inheritance in some families, and localize this gene to a region of ≈7 centiMorgans, in close proximity to the locus for multiple endocrine neoplasia type 2 (MEN2).

A genetic study of Hirschsprung disease.

A model of gene action with random effects during morphogenesis is compatible with observations, and an increased sex ratio and an elevated risk to sibs are observed.

Adult-onset Hirschsprung's disease.

A 53-year-old man who showed symptoms of aganglionic megacolon late in life, perhaps made clinically apparent as a result of the use of antipsychotic medication is reported.

The genetics of Hirschsprung's disease. Evidence for heterogeneous etiology and a study of sixty-three families.

  • E. Passarge
  • Medicine
    The New England journal of medicine
  • 1967
It is necessary to select patients suitable for surgery for vaginal or laparoscopic mesh placement for Hirschsprung's disease preoperatively on the basis of prior history and once they provide informed consent for surgery.

Structural analysis of the human ret proto-oncogene using exon trapping.

A genomic contig of the human ret protooncogene was created with four overlapping cosmid clones isolated from two libraries and eight cosmid fragments were analysed in detail for the presence of ret exons using exon trapping.

Three‐generation transmission of Hirschsprung's disease

A three‐generation family with non‐syndromic biopsy‐proven Hirschsprung's disease involving both short and long segments of the large bowel is reported. Although this is the first three‐generation