{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T14:51:29Z","timestamp":1786546289430,"version":"build-2736575974"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Transl Gastroenterol","Clinical and Translational Gastroenterology"],"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVES:<\/jats:title>\n                    <jats:p>\n                      Loss-of-function mutations of\n                      <jats:italic toggle=\"yes\">BMPR1A<\/jats:italic>\n                      cause juvenile polyposis syndrome (JPS), but large genomic deletions in\n                      <jats:italic toggle=\"yes\">BMPR1A<\/jats:italic>\n                      are rare, reported in few families only, and data regarding the associated phenotype are limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We investigated clinical features and genomic data of 7 extended seemingly unrelated families with a genomic deletion of the entire coding region of\n                      <jats:italic toggle=\"yes\">BMPR1A<\/jats:italic>\n                      . We defined mutation size, mutation prevalence, and tumor pathogenesis using whole-genome sequencing, targeted genotyping, and haplotype analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Patients with JPS from 7 families of Bukharin Jewish ancestry carried a deletion of 429 kb, encompassing the\n                      <jats:italic toggle=\"yes\">BMPR1A<\/jats:italic>\n                      coding sequence and 8 downstream genes. Haplotype analysis and testing controls identified this as a common founder mutation occurring in 1\/124 individuals of Bukharin origin. Tumor testing did not demonstrate loss of heterozygosity. Among carriers, JPS was almost fully penetrant, but clinical features varied widely, ranging from mild to very severe, including pan-enteric polyps, gastritis, and colorectal, esophageal, and testicular cancer, and carriers with phenotypes, which would not have raised suspicion of JPS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION:<\/jats:title>\n                    <jats:p>The phenotype in this large cohort was extremely variable, although all carriers shared the same variant and the same genetic background. New observations include a preponderance of adenomatous rather than juvenile polyps, possible association with testicular cancer, and unexpected upper gastrointestinal involvement.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.14309\/ctg.0000000000000054","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T09:23:57Z","timestamp":1561713837000},"page":"e00054","source":"Crossref","is-referenced-by-count":12,"title":["Variable Features of Juvenile Polyposis Syndrome With Gastric Involvement Among Patients With a Large Genomic Deletion of BMPR1A"],"prefix":"10.14309","volume":"10","author":[{"given":"Sari","family":"Lieberman","sequence":"first","affiliation":[{"name":"Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Beeri","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Walsh","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Genome Sciences, University of Washington, Seattle, Washington, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menachem","family":"Schechter","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Shaare Zedek Medical Center, Jerusalem, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Keret","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Department, Clalit Health Services, Jerusalem, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabet","family":"Half","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Rambam Health Care Campus, Haifa, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suleyman","family":"Gulsuner","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Genome Sciences, University of Washington, Seattle, Washington, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariela","family":"Tomer","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold","family":"Jacob","sequence":"additional","affiliation":[{"name":"Institute of Gastroenterology and Liver Diseases, Hadassah Medical Center, Jerusalem, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlomi","family":"Cohen","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit, \u201cDana-Dwek\u201d Children's Hospital, Tel Aviv, Israel;"},{"name":"Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel;"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Basel-Salmon","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;"},{"name":"Raphael Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel;"},{"name":"Pediatric Genetics Clinic, Schneider Children's Medical Center of Israel, Petah Tikva, Israel;"},{"name":"Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmud","family":"Mansur","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Berger","sequence":"additional","affiliation":[{"name":"Maccabi Health Services, Rehovot, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lior H.","family":"Katz","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;"},{"name":"Department of Gastroenterology, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliahu","family":"Golomb","sequence":"additional","affiliation":[{"name":"Pathology Department, Shaare Zedek Medical Center, Jerusalem, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Peretz","sequence":"additional","affiliation":[{"name":"Sharett Institute of Oncology, Hebrew University\u2013Hadassah Medical Center, Jerusalem, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohar","family":"Levy","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;"},{"name":"Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inbal","family":"Kedar","sequence":"additional","affiliation":[{"name":"Raphael Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary-Claire","family":"King","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Genome Sciences, University of Washington, Seattle, Washington, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ephrat","family":"Levy-Lahad","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel;"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Raphael Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"R1-20230814","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1097\/DCR.0b013e31826278b3","article-title":"Juvenile polyposis syndrome: A study of genotype, phenotype, and long-term outcome","volume":"55","author":"Latchford","year":"2012","journal-title":"Dis Colon Rectum"},{"key":"R3-20230814","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1111\/j.1572-0241.2005.40237.x","article-title":"The hamartomatous polyposis syndromes: A clinical and molecular review","volume":"100","author":"Schreibman","year":"2005","journal-title":"Am J Gastroenterol"},{"key":"R4-20230814","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1038\/ajg.2009.542","article-title":"Germline bone morphogenesis protein receptor 1A mutation causes colorectal tumorigenesis in hereditary mixed polyposis syndrome","volume":"104","author":"Cheah","year":"2009","journal-title":"Am J Gastroenterol"},{"key":"R5-20230814","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.humpath.2015.10.002","article-title":"Morphologic characterization of hamartomatous gastrointestinal polyps in Cowden syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome","volume":"49","author":"Shaco-Levy","year":"2016","journal-title":"Hum Pathol"},{"key":"R6-20230814","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1136\/jmg.2007.052506","article-title":"High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome","volume":"44","author":"Aretz","year":"2007","journal-title":"J Med Genet"},{"key":"R7-20230814","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/bjs.9693","article-title":"Genotype-defined cancer risk in juvenile polyposis syndrome","volume":"102","author":"Aytac","year":"2015","journal-title":"Br J Surg"},{"key":"R8-20230814","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/BF02303487","article-title":"The risk of gastrointestinal carcinoma in familial juvenile polyposis","volume":"5","author":"Howe","year":"1998","journal-title":"Ann Surg Oncol"},{"key":"R9-20230814","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1136\/gut.2006.116913","article-title":"Risk of colorectal cancer in juvenile polyposis","volume":"56","author":"Brosens","year":"2007","journal-title":"Gut"},{"key":"R10-20230814","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/nrc3500","article-title":"Beyond TGF\u03b2: Roles of other TGF\u03b2 superfamily members in cancer","volume":"13","author":"Wakefield","year":"2013","journal-title":"Nat Rev Cancer"},{"key":"R11-20230814","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/gcc.22270","article-title":"Somatic alterations in juvenile polyps from BMPR1A and SMAD4 mutation carriers","volume":"54","author":"Blatter","year":"2015","journal-title":"Genes Chromosomes Cancer"},{"key":"R12-20230814","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1136\/gut.2007.142927","article-title":"Large genomic deletions of SMAD4, BMPR1A and PTEN in juvenile polyposis","volume":"57","author":"van Hattem","year":"2008","journal-title":"Gut"},{"key":"R13-20230814","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1399-0004.2008.01091.x","article-title":"The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis","volume":"75","author":"Calva-Cerqueira","year":"2009","journal-title":"Clin Genet"},{"key":"R14-20230814","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1086\/507151","article-title":"Deletion of PTEN and BMPR1A on chromosome 10q23 is not always associated with juvenile polyposis of infancy","volume":"79","author":"Salviati","year":"2006","journal-title":"Am J Hum Genet"},{"key":"R16-20230814","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/gim.2015.212","article-title":"Improving performance of multigene panels for genomic analysis of cancer predisposition","volume":"18","author":"Shirts","year":"2016","journal-title":"Genet Med"},{"key":"R17-20230814","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/1471-2164-12-184","article-title":"Accurate and exact CNV identification from targeted high-throughput sequence data","volume":"12","author":"Nord","year":"2011","journal-title":"BMC Genomics"},{"key":"R19-20230814","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1093\/bioinformatics\/btt314","article-title":"Isaac: Ultra-fast whole-genome secondary analysis on Illumina sequencing platforms","volume":"29","author":"Raczy","year":"2013","journal-title":"Bioinformatics"},{"key":"R20-20230814","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1093\/bioinformatics\/btr670","article-title":"Control-FREEC: A tool for assessing copy number and allelic content using next-generation sequencing data","volume":"28","author":"Boeva","year":"2012","journal-title":"Bioinformatics"},{"key":"R21-20230814","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"R22-20230814","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1158\/1940-6207.CAPR-11-0080","article-title":"Frequency of rearrangements in Lynch syndrome cases associated with MSH2: Characterization of a new deletion involving both EPCAM and the 5\u2032 part of MSH2","volume":"4","author":"P\u00e9rez-Cabornero","year":"2011","journal-title":"Cancer Prev Res"},{"key":"R23-20230814","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s00439-017-1766-y","article-title":"Emerging genotype-phenotype relationships in patients with large NF1 deletions","volume":"136","author":"Kehrer-Sawatzki","year":"2017","journal-title":"Hum Genet"}],"container-title":["Clinical and Translational Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/01720094-201907000-00005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:54:43Z","timestamp":1786542883000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01720094-201907000-00005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,1]]},"references-count":20,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.14309\/ctg.0000000000000054","relation":{},"ISSN":["2155-384X"],"issn-type":[{"value":"2155-384X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,1]]}}}