Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases
| Autor: | Malcolm G. Dunlop, Barbara A. Leggett, David Markie, Diana Eccles, Stephen Bevan, R. K. S. Phillips, Charis Eng, K Neale, Richard S. Houlston, Andrew Williams, Takeo Iwama, Miguel A. Rodriguez-Bigas, Kelly Woodford-Richens, Eamon Sheridan, Walter F. Bodmer, Joanne P. Young, Ian Tomlinson, Shirley Hodgson, Paul Rozen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Male
Candidate gene Biology medicine.disease_cause Germline Frameshift mutation Germline mutation Genetics medicine Humans Missense mutation Genes Tumor Suppressor Juvenile polyposis syndrome Molecular Biology Germ-Line Mutation Genetics (clinical) Gastrointestinal Neoplasms Smad4 Protein Mutation Genetic heterogeneity Intestinal Polyps General Medicine medicine.disease digestive system diseases Pedigree DNA-Binding Proteins Haplotypes Trans-Activators Female Lod Score Hamartoma Syndrome Multiple Microsatellite Repeats |
| Zdroj: | Human molecular genetics. 7(12) |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | Juvenile polyps are present in a number of Mendelian disorders, sometimes in association only with gastrointestinal cancer [juvenile polyposis syndrome (JPS)] and sometimes as part of known syndromes (Cowden, Gorlin and Banayan-Zonana) in association with developmental abnormalities, dysmorphic features or extra-intestinal tumours. Recently, a gene for JPS was mapped to 18q21.1 and the candidate gene DPC4 (SMAD4) was shown to carry frameshift mutations in some JPS families. We have analysed eight JPS families for linkage to DPC4. Overall, there was no evidence for linkage to DPC4; linkage could be excluded in two of the eight pedigrees and was unlikely in two others. We then tested these eight families and a further 13 familial and sporadic JPS cases for germline mutations in DPC4. Just one germline DPC4 mutation was found (in a familial JPS patient from a pedigree unsuitable for linkage analysis). Like all three previously reported germline mutations, this variant occurred towards the C-terminus of the DPC4 protein. However, our patient's mutation is a missense change (R361C); somatic missense mutations in DPC4 have been reported previously in tumours. We therefore confirm DPC4 as a cause of JPS, but show that there is considerable remaining, uncharacterized genetic heterogeneity in this disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|