Investigation of germline GFRα-1 mutations in Hirschsprung disease
- Shirley M Myersa,
- Remi Salomonb,
- Antje Goesslingc,d,
- Anna Peletb,
- Charis Engd,
- Andreas von Deimlingc,
- Stanislas Lyonnetb,
- Lois M Mulligana
- aDepartments of Pathology and Paediatrics, Queen’s University, 20 Barrie Street, Kingston, Ontario K7L 3N6, Canada, bHôpital des Enfants Malades, Tour Technique Lavoisier, 149 rue de Sevres, 75743 Paris Cedex 15, France, cInstitut für Neuropathologie, Sigmund-Freud-Strasse 25, Universitätskliniken Bonn, 53105 Bonn, Germany, dTranslational Research Laboratory, Charles A Dana Human Cancer Genetics Unit, Dana-Farber Cancer Institute, The Susan and Richard Smith Laboratories, 1 Jimmy Fund Way, Boston, MA 02115-6084, USA
- Dr Mulligan.
- Received 27 April 1998
- Revised 31 July 1998
Abstract
Inactivating mutations of the RET proto-oncogene and of one of its soluble ligand molecules, glial cell line derived neurotrophic factor (GDNF), have been found in a subset of patients with Hirschsprung disease (HSCR). However, the majority of HSCR mutations remain unidentified. As normal RET function requires a multicomponent ligand complex for activation, other members of the RET ligand complex are primary candidates for these mutations. We investigated the presence of mutations in another member of the RET signalling complex, GDNF family receptor alpha-1 (GFRα-1), in a panel of 269 independent cases of HSCR. We identified 10 polymorphisms at the GFRα-1 locus. Surprisingly, however, we did not identify any sequence variants in our HSCR population that were not also present in a normal control population. Our data suggest that mutations of the GFRα-1 gene are not a common aetiological event in HSCR.
