Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes.
Juvenile polyposis syndrome (JPS) is an inherited hamartomatous-polyposis syndrome with a risk for colon cancer. JPS is a clinical diagnosis by exclusion, and, before susceptibility genes were identified, JPS could easily be confused with other inherited hamartoma syndromes, such as Bannayan-Riley-R...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2001
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| _version_ | 1797074599013253120 |
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| author | Zhou, X Woodford-Richens, K Lehtonen, R Kurose, K Aldred, M Hampel, H Launonen, V Virta, S Pilarski, R Salovaara, R Bodmer, W Conrad, B Dunlop, M Hodgson, S Iwama, T Järvinen, H Kellokumpu, I Kim, J Leggett, B Markie, D Mecklin, J Neale, K Phillips, R Piris, J Rozen, P |
| author_facet | Zhou, X Woodford-Richens, K Lehtonen, R Kurose, K Aldred, M Hampel, H Launonen, V Virta, S Pilarski, R Salovaara, R Bodmer, W Conrad, B Dunlop, M Hodgson, S Iwama, T Järvinen, H Kellokumpu, I Kim, J Leggett, B Markie, D Mecklin, J Neale, K Phillips, R Piris, J Rozen, P |
| author_sort | Zhou, X |
| collection | OXFORD |
| description | Juvenile polyposis syndrome (JPS) is an inherited hamartomatous-polyposis syndrome with a risk for colon cancer. JPS is a clinical diagnosis by exclusion, and, before susceptibility genes were identified, JPS could easily be confused with other inherited hamartoma syndromes, such as Bannayan-Riley-Ruvalcaba syndrome (BRRS) and Cowden syndrome (CS). Germline mutations of MADH4 (SMAD4) have been described in a variable number of probands with JPS. A series of familial and isolated European probands without MADH4 mutations were analyzed for germline mutations in BMPR1A, a member of the transforming growth-factor beta-receptor superfamily, upstream from the SMAD pathway. Overall, 10 (38%) probands were found to have germline BMPR1A mutations, 8 of which resulted in truncated receptors and 2 of which resulted in missense alterations (C124R and C376Y). Almost all available component tumors from mutation-positive cases showed loss of heterozygosity (LOH) in the BMPR1A region, whereas those from mutation-negative cases did not. One proband with CS/CS-like phenotype was also found to have a germline BMPR1A missense mutation (A338D). Thus, germline BMPR1A mutations cause a significant proportion of cases of JPS and might define a small subset of cases of CS/BRRS with specific colonic phenotype. |
| first_indexed | 2024-03-06T23:38:33Z |
| format | Journal article |
| id | oxford-uuid:6e7e53a4-1eda-4369-8311-4c1521bcf2c3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:38:33Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:6e7e53a4-1eda-4369-8311-4c1521bcf2c32022-03-26T19:24:58ZGermline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6e7e53a4-1eda-4369-8311-4c1521bcf2c3EnglishSymplectic Elements at Oxford2001Zhou, XWoodford-Richens, KLehtonen, RKurose, KAldred, MHampel, HLaunonen, VVirta, SPilarski, RSalovaara, RBodmer, WConrad, BDunlop, MHodgson, SIwama, TJärvinen, HKellokumpu, IKim, JLeggett, BMarkie, DMecklin, JNeale, KPhillips, RPiris, JRozen, PJuvenile polyposis syndrome (JPS) is an inherited hamartomatous-polyposis syndrome with a risk for colon cancer. JPS is a clinical diagnosis by exclusion, and, before susceptibility genes were identified, JPS could easily be confused with other inherited hamartoma syndromes, such as Bannayan-Riley-Ruvalcaba syndrome (BRRS) and Cowden syndrome (CS). Germline mutations of MADH4 (SMAD4) have been described in a variable number of probands with JPS. A series of familial and isolated European probands without MADH4 mutations were analyzed for germline mutations in BMPR1A, a member of the transforming growth-factor beta-receptor superfamily, upstream from the SMAD pathway. Overall, 10 (38%) probands were found to have germline BMPR1A mutations, 8 of which resulted in truncated receptors and 2 of which resulted in missense alterations (C124R and C376Y). Almost all available component tumors from mutation-positive cases showed loss of heterozygosity (LOH) in the BMPR1A region, whereas those from mutation-negative cases did not. One proband with CS/CS-like phenotype was also found to have a germline BMPR1A missense mutation (A338D). Thus, germline BMPR1A mutations cause a significant proportion of cases of JPS and might define a small subset of cases of CS/BRRS with specific colonic phenotype. |
| spellingShingle | Zhou, X Woodford-Richens, K Lehtonen, R Kurose, K Aldred, M Hampel, H Launonen, V Virta, S Pilarski, R Salovaara, R Bodmer, W Conrad, B Dunlop, M Hodgson, S Iwama, T Järvinen, H Kellokumpu, I Kim, J Leggett, B Markie, D Mecklin, J Neale, K Phillips, R Piris, J Rozen, P Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes. |
| title | Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes. |
| title_full | Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes. |
| title_fullStr | Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes. |
| title_full_unstemmed | Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes. |
| title_short | Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes. |
| title_sort | germline mutations in bmpr1a alk3 cause a subset of cases of juvenile polyposis syndrome and of cowden and bannayan riley ruvalcaba syndromes |
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