A rare haplotype of the RET proto-oncogene is a risk-modifying allele in Hirschsprung disease
| Jazyk: | English |
|---|---|
| ISSN: | 0002-9297 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d397a4459136640b490080fabc98f10f https://hdl.handle.net/11370/9c99e261-2d46-4e39-b06f-be6c3e57d4c8 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....d397a4459136640b490080fabc98f10f |
| Autor: | Barbara Pesce, Jan Osinga, Giovanna Patrone, Robert M.W. Hofstra, Francesca Puppo, Roberto Ravazzolo, Marcella Devoto, Paola Griseri, Monica Sancandi, Isabella Ceccherini, Giovanni Romeo |
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
EXPRESSION
endocrine system diseases Gene Expression TYROSINE KINASE ISOFORMS RET proto-oncogene Biology Proto-Oncogene Mas Genetic determinism Exon 3'-SPLICING VARIANTS MISSENSE MUTATION Proto-Oncogene Proteins Report medicine Genetics Drosophila Proteins Humans Genetics(clinical) Hirschsprung Disease RNA Messenger Allele Genetics (clinical) Alleles Haplotype Proto-Oncogene Proteins c-ret Genetic disorder Receptor Protein-Tyrosine Kinases PROTOONCOGENE medicine.disease Penetrance Pedigree Haplotypes Cancer research |
| Zdroj: | American Journal of Human Genetics, 71(4), 969-974. CELL PRESS Scopus-Elsevier |
| ISSN: | 0002-9297 |
| Popis: | Hirschsprung disease (HSCR) is a common genetic disorder characterized by intestinal obstruction secondary to enteric aganglionosis. HSCR demonstrates a complex pattern of inheritance, with the RET proto-oncogene acting as a major gene and with several additional susceptibility loci related to the Ret-signaling pathway or to other developmental programs of neural crest cells. To test how the HSCR phenotype may be affected by the presence of genetic variants, we investigated the role of a single-nucleotide polymorphism (SNP), 2508C-->T (S836S), in exon 14 of the RET gene, characterized by low frequency among patients with HSCR and overrepresentation in individuals affected by sporadic medullary thyroid carcinoma. Typing of several different markers across the RET gene demonstrated that a whole conserved haplotype displayed anomalous distribution and nonrandom segregation in families with HSCR. We provide genetic evidence about a protective role of this low-penetrant haplotype in the pathogenesis of HSCR and demonstrate a possible functional effect linked to RET messenger RNA expression. |
| Databáze: | OpenAIRE |
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