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[Molecular genetics of Hirschsprung disease: a model of multigenic neurocristopathy].
J Soc Biol. 2000; 194(3-4):125-8.JS

Abstract

Hirschsprung's disease (HSCR, aganglionic megacolon) is a frequent congenital malformation regarded as a multigenic neurocristopathy. Three susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene, the endothelin B receptor (EDNRB) gene, and the endothelin 3 (EDN3) gene. RET gene mutations were found in significant proportions of familial (50%) and sporadic (15-20%) HSCR, while homozygosity for EDNRB or EDN3 mutations accounted for the rare HSCR-Waardenburg syndrome (WS) association. More recently, heterozygous EDNRB an EDN3 missense mutations have been reported in isolated HSCR patients. Some of these results were obtained after the identification of mouse genes whose natural or site-directed mutations resulted in megacolon and coat color spotting. There is also conclusive evidence for the involvement of other independent loci in HSCR. In particular, the recent identification of neurotrophic factors acting as RET ligands (GDNF and Neurturin) provide additional candidate genes for HSCR. The dissection of the genetic etiology of HSCR disease may then provide a unique opportunity to distinguish between a polygenic and a genetically heterogeneous disease, thereby helping to understand other complex disorders and congenital malformations hitherto considered as multifactorial in origin. Finally, the study of the molecular bases of HSCR is also a step towards the understanding of developmental genetics of the enteric nervous system giving support to the role of the tyrosine kinase and endothelin-signaling pathways in the development of neural crest-derived enteric neurons in human.

Authors+Show Affiliations

Département de Génétique, Unité INSERM U-393, et Clinique Chirurgicale Infantile Hôpital Necker-Enfants Malades, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Review

Language

fre

PubMed ID

11324313

Citation

Amiel, J, et al. "[Molecular Genetics of Hirschsprung Disease: a Model of Multigenic Neurocristopathy]." Journal De La Societe De Biologie, vol. 194, no. 3-4, 2000, pp. 125-8.
Amiel J, Salomon R, Attié-Bitach T, et al. [Molecular genetics of Hirschsprung disease: a model of multigenic neurocristopathy]. J Soc Biol. 2000;194(3-4):125-8.
Amiel, J., Salomon, R., Attié-Bitach, T., Touraine, R., Steffann, J., Pelet, A., Nihoul-Fékété, C., Vekemans, M., Munnich, A., & Lyonnet, S. (2000). [Molecular genetics of Hirschsprung disease: a model of multigenic neurocristopathy]. Journal De La Societe De Biologie, 194(3-4), 125-8.
Amiel J, et al. [Molecular Genetics of Hirschsprung Disease: a Model of Multigenic Neurocristopathy]. J Soc Biol. 2000;194(3-4):125-8. PubMed PMID: 11324313.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Molecular genetics of Hirschsprung disease: a model of multigenic neurocristopathy]. AU - Amiel,J, AU - Salomon,R, AU - Attié-Bitach,T, AU - Touraine,R, AU - Steffann,J, AU - Pelet,A, AU - Nihoul-Fékété,C, AU - Vekemans,M, AU - Munnich,A, AU - Lyonnet,S, PY - 2001/4/28/pubmed PY - 2001/5/25/medline PY - 2001/4/28/entrez SP - 125 EP - 8 JF - Journal de la Societe de biologie JO - J Soc Biol VL - 194 IS - 3-4 N2 - Hirschsprung's disease (HSCR, aganglionic megacolon) is a frequent congenital malformation regarded as a multigenic neurocristopathy. Three susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene, the endothelin B receptor (EDNRB) gene, and the endothelin 3 (EDN3) gene. RET gene mutations were found in significant proportions of familial (50%) and sporadic (15-20%) HSCR, while homozygosity for EDNRB or EDN3 mutations accounted for the rare HSCR-Waardenburg syndrome (WS) association. More recently, heterozygous EDNRB an EDN3 missense mutations have been reported in isolated HSCR patients. Some of these results were obtained after the identification of mouse genes whose natural or site-directed mutations resulted in megacolon and coat color spotting. There is also conclusive evidence for the involvement of other independent loci in HSCR. In particular, the recent identification of neurotrophic factors acting as RET ligands (GDNF and Neurturin) provide additional candidate genes for HSCR. The dissection of the genetic etiology of HSCR disease may then provide a unique opportunity to distinguish between a polygenic and a genetically heterogeneous disease, thereby helping to understand other complex disorders and congenital malformations hitherto considered as multifactorial in origin. Finally, the study of the molecular bases of HSCR is also a step towards the understanding of developmental genetics of the enteric nervous system giving support to the role of the tyrosine kinase and endothelin-signaling pathways in the development of neural crest-derived enteric neurons in human. SN - 1295-0661 UR - https://www.unboundmedicine.com/medline/citation/11324313/[Molecular_genetics_of_Hirschsprung_disease:_a_model_of_multigenic_neurocristopathy]_ DB - PRIME DP - Unbound Medicine ER -