caa a22 4500 397575084 CHVBK 20180308164853.0 cr unu---uuuuu 161202e199612 xx s 000 0 eng 10.1093/hmg/5.12.2023 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.12.2023 De Novo Mutation of GDNF, Ligand for the RET/GDNFR-α Receptor Complex, in Hirschsprung Disease [Elektronische Daten] [Stacey M. Ivanchuk, Shirley M. Myers, Charis Eng, Lois M. Mulligan] Hirschsprung disease (HSCR) is a common congenital abnormality characterized by absence of the enteric ganglia in the hind gut. In 10-40% of HSCR cases, mutations of the RET receptor tyrosine kinase have been found. The recent identification of a multimeric RET ligand/receptor complex suggested that mutations of genes encoding other components of this complex might also occur in HSCR. To investigate this role, we examined the gene for glial cell line-derived neurotrophic factor (GDNF), the circulating ligand of the RET receptor complex, for mutations in a panel of sporadic and familial HSCR. We identified GDNF sequence variants in 2/36 HSCR patients. The first of these was a conservative change which did not affect the GDNF protein sequence. The second variant was a de novo missense mutation in a family with no history of HSCR and without mutation of the RET gene. Thus, our data are consistent with a causative role for GDNF mutations in some HSCR cases. © 1993 Oxford University Press Ivanchuk Stacey M. Departments of Pathology and Paediatrics, Queen's University, Kingston, ON, K7L 3N6, Canada aut Myers Shirley M. Departments of Pathology and Paediatrics, Queen's University, Kingston, ON, K7L 3N6, Canada aut Eng Charis Division of Cancer Epidemiology and Control, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 0211-56084, USA aut Mulligan Lois M. Departments of Pathology and Paediatrics, Queen's University, Kingston, ON, K7L 3N6, Canada aut Human Molecular Genetics Oxford University Press 5/12(1996-12), 2023-2026 0964-6906 5:12<2023 1996 5 hmg https://doi.org/10.1093/hmg/5.12.2023 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.12.2023 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ivanchuk Stacey M. Departments of Pathology and Paediatrics, Queen's University, Kingston, ON, K7L 3N6, Canada aut NATIONALLICENCE 700 1- Myers Shirley M. Departments of Pathology and Paediatrics, Queen's University, Kingston, ON, K7L 3N6, Canada aut NATIONALLICENCE 700 1- Eng Charis Division of Cancer Epidemiology and Control, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 0211-56084, USA aut NATIONALLICENCE 700 1- Mulligan Lois M. Departments of Pathology and Paediatrics, Queen's University, Kingston, ON, K7L 3N6, Canada aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/12(1996-12), 2023-2026 0964-6906 5:12<2023 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford