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

@article{Angrist1993AGF,
  title={A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10},
  author={Misha Angrist and Erick R. Kauffman and Susan A. Slaugenhaupt and Tara Cox Matise and Erik G. Puffenberger and Sarah S. Washington and Anthony H. Lipson and Daniel T. Cass and Troy Reyna and Daniel E. Weeks and William Sieber and Aravinda Chakravarti},
  journal={Nature Genetics},
  year={1993},
  volume={4},
  pages={351-356}
}
Hirschsprung disease (HSCR) is characterized by a congenital absence of enteric ganglia along a variable length of the intestine. Although long considered to be a multifactorial disease, we have identified linkage in a subset of five HSCR families to the pericentromeric region of chromosome 10, thereby proving monogenic inheritance in some families. A maximum two–point lod score of 3.37 (\[thetacirc] = 0.045) was observed between HSCR and D10S176, under an incompletely penetrant dominant model… 
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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.
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.
Hirschsprung disease, associated syndromes and genetics: a review
TLDR
Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment, which stands as a model for genetic disorders with complex patterns of inheritance.
Association study of PHOX2B as a candidate gene for Hirschsprung’s disease
TLDR
The PHOX2B A→G1364 polymorphism is associated with HSCR, and whether it directly contributes to disease susceptibility or represents a marker for a locus in LD with PHox2B needs further investigation.
A human model for multigenic inheritance: phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus.
TLDR
Although the presence of RET mutations in group I families is sufficient to explain HSCR inheritance, a genome scan reveals a new susceptibility locus on 9q31 exclusively in group II families, implying that identification of new susceptibility factors in a complex disease may depend on classification of families by mutational type at known susceptibility genes.
Identification of Variants in RET and IHH Pathway Members in a Large Family With History of Hirschsprung Disease.
TLDR
In a study of a large family with history of HSCR, variants in LRBA, RET, the gene encoding the RET ligand (GDNF), IHH, and a gene encoding a mediator of IHH signaling (GLI3) reduced the number of enteric neurons in the zebrafish gut.
Hirschsprung’s disease: genetic mutations in mice and men
TLDR
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.
Hirschsprung's disease associated with a deletion of chromosome 10 (q11.2q21.2): a further link with the neurocristopathies?
TLDR
A patient with total colonic aganglionosis in association with a deletion of part of the long arm of chromosome 10 includes the ret proto-oncogene, which has recently been implicated in multiple endocrine neoplasia type 2A (MEN 2A).
Endothelin-B receptor mutations in patients with isolated Hirschsprung disease from a non-inbred population.
TLDR
DNA samples from 17 probands of Italian origin with HSCR are analysed and two novel EDNRB mutations are identified, confirming the involvement ofEDNRB in HSCRs pathogenesis and demonstrating that EDNRBs mutations could contribute to HSCr disease in non-inbred populations.
Gastrointestinal Tract: Molecular Genetics of Hirschsprung Disease
TLDR
Nine genes and three signal pathways have been identified in relation to the aetiology of this group of disorders, and Hirschsprung disease is currently the best understood multifactorial, nonMendelian genetic disorder.
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References

SHOWING 1-10 OF 45 REFERENCES
Deleted and normal chromosome 10 homologs from a patient with Hirschsprung disease isolated in two cell hybrids through enrichment by immunomagnetic selection.
TLDR
A cytogenetically undetectable deletion was observed in a patient with total colonic aganglionosis with small bowel involvement (TCSA), a variant of Hirschsprung disease, and it is hypothesized that they originate from mutations in different genes clustered in the centromeric region of 10q.
Improved predictive test for MEN2, using flanking dinucleotide repeats and RFLPs.
TLDR
A new genetic linkage map of the pericentromeric region of chromosome 10 is constructed, on the basis of 13 polymorphisms at six loci, which places the MEN2A locus between the dinucleotide repeat markers, with odds of 5,750:1 over the next most likely position.
Association of megacolon with a new dominant spotting gene (Dom) in the mouse.
TLDR
A new semidominant mutation in the mouse is described that produces white spotting and a deficiency of myenteric ganglion cells in the colon and, in homozygotes, is lethal prior to 13 days of gestation.
Identification and characterization of a gene at D10S94 in the MEN2A region.
A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10
TLDR
This work has reported linkage between the MEN2A locus and the interstitial retinol-binding protein gene, which is located on chromosome 10p11.2-q11.3, and Simpson et al.2 recently reported preliminary evidence for linkage Between the DNA probe p9-12A on chromosomes 10 and MEN2a.
Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene
TLDR
It is shown that some families with WS have mutations in the human homologue9 of Pax-3, which is one of a family of eight Pax genes known in mice which are involved in regulating embryonic development and which contains a highly conserved transcription control sequence, the paired box.
Assignment of multiple endocrine neoplasia type 2A to chromosome 10 by linkage
TLDR
The MEN2A locus was assigned to chromosome 10 by linkage with a new DNA marker (D10S5) and the linkage led to investigate other chromosome 10 markers and demonstrate linkage between the disease locus and the interstitial retinol-binding protein (IRBP) gene1.
A cluster of expressed zinc finger protein genes in the pericentromeric region of human chromosome 10.
A genetic study of Hirschsprung disease.
TLDR
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.
Presymptomatic identification of carriers of the multiple endocrine neoplasia type 2A gene using flanking DNA markers.
TLDR
It is concluded that genetic testing with flanking DNA markers is a highly accurate method for the presymptomatic identification of MEN2A gene carriers and allows for diagnosis at an earlier stage than does traditional calcitonin testing.
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