Novel intronic polymorphisms in theRET proto-oncogene and their association with Hirschsprung disease
| Autor: | Andreas Ziegler, Hans K. Schackert, Guido Fitze, Dietmar Roesner, Matthias Schreiber, Eberhard Kuhlisch, Mandy Schierz |
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| Rok vydání: | 2003 |
| Předmět: |
Male
endocrine system diseases Multiple endocrine neoplasia type 2 Biology RET proto-oncogene Proto-Oncogene Mas Germline mutation Proto-Oncogene Proteins Genotype Genetics medicine Humans Hirschsprung Disease Allele frequency Genetics (clinical) Polymorphism Genetic Proto-Oncogene Proteins c-ret Haplotype Receptor Protein-Tyrosine Kinases medicine.disease Phenotype Introns Female |
| Zdroj: | Human Mutation. 22:177-177 |
| ISSN: | 1098-1004 1059-7794 |
| DOI: | 10.1002/humu.9161 |
| Popis: | Germline mutations of the RET proto-oncogene have been found in familial and sporadic forms of Hirschsprung disease (HSCR), but also in the autosomal dominantly inherited multiple endocrine neoplasia type 2 (MEN2) syndromes, which comprise the medullary thyroid carcinoma (MTC) as an obligatory feature. Besides mutations various polymorphisms of the RET proto-oncogene are associated with the HSCR. In this study, we have characterized seven intronic RET polymorphisms (IVS2+9G>A, IVS4+48A>G, IVS12+47C>T, IVS14-24G>A, IVS19+47T>C, IVS20+96C>T, 3'UTR+124A>G) and investigated these variants by DNA sequencing in populations of 76 HSCR patients and 40 sporadic MTC patients as well as in a control population. Variants of four of these seven polymorphisms have a strong association with the HSCR phenotype. In contrast, none of the investigated polymorphisms show a significant difference in the genotype distribution and the allele frequencies in patients with sporadic MTC when compared to controls. These findings support the hypothesis that specific RET haplotypes cause or modify the HSCR phenotype. |
| Databáze: | OpenAIRE |
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