Journal Article

<i>De Novo</i> Mutation of GDNF, Ligand for the RET/GDNFR-α Receptor Complex, in Hirschsprung Disease

Stacey M. Ivanchuk, Shirley M. Myers, Charis Eng and Lois M. Mulligan

in Human Molecular Genetics

Volume 5, issue 12, pages 2023-2026
Published in print December 1996 | ISSN: 0964-6906
e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/5.12.2023
De Novo Mutation of GDNF, Ligand for the RET/GDNFR-α Receptor Complex, in Hirschsprung Disease

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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.

Journal Article.  2798 words.  Illustrated.

Subjects: Genetics and Genomics

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