BACKGROUND: Hirschsprung disease (HSCR) is a developmental disorder caused by a defect in the neural crest neuroblast migration process. It is considered to be a paradigm of complex disorders, with many loci contributing to manifestation of the disease. Although HSCR commonly appears as a sporadic trait, approximately 20% of HSCR cases are familial, with complex patterns of inheritance. METHOD: A multiplex HSCR family with an additive model of inheritance, in which the contribution of three genes (RET, NTRK3, EDN3) leads to the HSCR phenotype is reported. RESULTS AND DISCUSSION: The findings suggest that both RET and NTRK3 mutations acting together are necessary and sufficient for the appearance of the disease, and that the EDN3 mutation is acting as a phenotype-modifier factor in the context of this family, as two different HSCR phenotypes are seen among the affected members: a short segment form, and a total colonic aganglionosis. The results therefore support the complex additive model of inheritance previously proposed for Hirschsprung disease.
BACKGROUND:Hirschsprung disease (HSCR) is a developmental disorder caused by a defect in the neural crest neuroblast migration process. It is considered to be a paradigm of complex disorders, with many loci contributing to manifestation of the disease. Although HSCR commonly appears as a sporadic trait, approximately 20% of HSCR cases are familial, with complex patterns of inheritance. METHOD: A multiplex HSCR family with an additive model of inheritance, in which the contribution of three genes (RET, NTRK3, EDN3) leads to the HSCR phenotype is reported. RESULTS AND DISCUSSION: The findings suggest that both RET and NTRK3 mutations acting together are necessary and sufficient for the appearance of the disease, and that the EDN3 mutation is acting as a phenotype-modifier factor in the context of this family, as two different HSCR phenotypes are seen among the affected members: a short segment form, and a total colonic aganglionosis. The results therefore support the complex additive model of inheritance previously proposed for Hirschsprung disease.
Authors: David N Cooper; Michael Krawczak; Constantin Polychronakos; Chris Tyler-Smith; Hildegard Kehrer-Sawatzki Journal: Hum Genet Date: 2013-07-03 Impact factor: 4.132
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Authors: Berta Luzón-Toro; Hongsheng Gui; Macarena Ruiz-Ferrer; Clara Sze-Man Tang; Raquel M Fernández; Pak-Chung Sham; Ana Torroglosa; Paul Kwong-Hang Tam; Laura Espino-Paisán; Stacey S Cherny; Marta Bleda; María Del Valle Enguix-Riego; Joaquín Dopazo; Guillermo Antiñolo; María-Mercé García-Barceló; Salud Borrego Journal: Sci Rep Date: 2015-11-12 Impact factor: 4.379