title: Mutations in SCG10 are not involved in Hirschsprung disease.
abstract: Hirschsprung disease (HSCR) is a congenital malformation characterized by the absence of enteric neurons in the distal part of the colon. Several genes have been implicated in the development of this disease that together account for 20% of all cases, implying that other genes are involved. Since HSCR is frequently associated with other congenital malformations, the functional characterization of the proteins encoded by the genes involved in these syndromes can provide insights into the protein-network involved in HSCR development. Recently, we found that KBP, encoded by the gene involved in a HSCR- associated syndrome called Goldberg-Shprintzen syndrome, interacts with SCG10, a stathmin-like protein. To determine if SCG10 is involved in the etiology of HSCR, we determined SCG10 expression levels during development and screened 85 HSCR patients for SCG10 mutations. We showed that SCG10 expression increases during development but no germline mutation was found in any of these patients. In conclusion, this study shows that SCG10 is not directly implicated in HSCR development. However, an indirect involvement of SCG10 cannot be ruled out as this can be due to a secondary effect caused by its direct interactors.
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Maria M M
authors.initials: MM
authors.lastname: Alves
authors.forename: Jan
authors.initials: J
authors.lastname: Osinga
authors.forename: Joke B G M
authors.initials: JB
authors.lastname: Verheij
authors.forename: Marco
authors.initials: M
authors.lastname: Metzger
authors.forename: Bart J L
authors.initials: BJ
authors.lastname: Eggen
authors.forename: Robert M W
authors.initials: RM
authors.lastname: Hofstra
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D018095:Germ-Line Mutation; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009432:Neural Crest / Q000166:cytology; D025941:Protein Interaction Mapping; D050777:Stathmin; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors
chemical_list: D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050777:Stathmin; C512849:Stmn2 protein, mouse