title: Molecular genetics of colorectal motility disorders.
abstract: In the last years, several genes have been identified which are involved in the development and differentiation of the enteric nervous system (ENS). Among the congenital intestinal innervation disorders described (aganglionosis, hypoganglionosis, heterotopic ganglia, intestinal neuronal dysplasia), up to now Hirschsprung's disease (HSCR) has been linked to mutational defects in these genes. GDNF and its co-receptor RET are the genes with the most mitogene potency on precursor cells of the ENS. The endothelin system (EDNRB/EDN3) also plays a key role in the development of the ENS by preventing its premature differentiation. Our own studies could show that, whereas a homozygous mutation of EDNRB causes long-segment HSCR, a heterozygous EDNRB deficiency leads to alterations of the ENS resembling the histopathology observed in intestinal neuronal dysplasia. Modern molecular genetic technologies combined with a subtle phenotypic assessment of the ENS will allow investigators to identify other genes within the complex signalling cascade required for the formation of the ENS. The recognition that intestinal innervation disorders are, at least in part, a multigenetic disease should provide support for consequent genetic screening in these patients.
authors.affiliation: Department of Paediatric Surgery, University Hospital of Heidelberg at Mannheim, Theodor-Kutzer-Strasse 1-3, 68135 Mannheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Holland-Cunz
authors.forename: H-J
authors.initials: HJ
authors.lastname: Krammer
authors.forename: A
authors.initials: A
authors.lastname: Süss
authors.forename: K
authors.initials: K
authors.lastname: Tafazzoli
authors.forename: T
authors.initials: T
authors.lastname: Wedel
mesh_terms: D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000151:congenital / Q000235:genetics* / Q000503:physiopathology; D016232:Endothelins / Q000378:metabolism; D017615:Enteric Nervous System / Q000196:embryology* / Q000254:growth & development / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000235:genetics*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006579:Heterozygote; D006627:Hirschsprung Disease / Q000235:genetics* / Q000503:physiopathology; D006720:Homozygote; D007410:Intestinal Diseases / Q000151:congenital / Q000235:genetics* / Q000503:physiopathology; D007422:Intestines / Q000294:innervation*; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases; D044023:Receptor, Endothelin B / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor
chemical_list: D016232:Endothelins; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D044023:Receptor, Endothelin B; D017475:Receptors, Nerve Growth Factor; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C495001:Ret protein, rat