{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:14:46Z","timestamp":1773278086706,"version":"3.50.1"},"reference-count":23,"publisher":"BMJ","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[1999,7,22]]},"published-print":{"date-parts":[[1999,10,1]]},"abstract":"<jats:p>Hirschsprung disease (HSCR) is a common genetic disorder presenting with functional intestinal obstruction secondary to enteric aganglionosis. HSCR can be familial or sporadic. Although five putative susceptibility genes have been identified, only germline mutations in the <jats:italic>RET<\/jats:italic> proto-oncogene account for a significant minority (up to 50%) of familial HSCR; 3% of sporadic HSCR in a population based series carry <jats:italic>RET<\/jats:italic>mutations. From 1998 to February 1999, we prospectively ascertained 64 cases of sporadic HSCR from the western Andalusia region. To determine if polymorphic sequence variants within <jats:italic>RET<\/jats:italic>could act as low penetrance predisposing alleles, we examined allelic frequencies at seven polymorphic loci in this population based series. Whether allele frequencies differed from those in the control population were determined by either chi-squared analysis or Fisher\u2019s exact test. For two sequence variants, A45A (c 135G\u2192A) (exon 2) and L769L (c 2307T\u2192G) (exon 13), the rarer polymorphic allele was over-represented among HSCR cases versus controls (p&lt;0.0006). In contrast, two other polymorphisms, G691S (c 2071C\u2192A) (exon 11) and S904S (c 2712C\u2192G) (exon 15), were under-represented in the HSCR patients compared to controls (p=0.02). Polymorphisms in the<jats:italic>RET<\/jats:italic> proto-oncogene appear to predispose to HSCR in a complex, low penetrance fashion and may also modify phenotypic expression.<\/jats:p>","DOI":"10.1136\/jmg.36.10.771","type":"journal-article","created":{"date-parts":[[2013,2,15]],"date-time":"2013-02-15T13:28:56Z","timestamp":1360934936000},"page":"771-774","source":"Crossref","is-referenced-by-count":111,"title":["Specific polymorphisms in the <i>RET<\/i>proto-oncogene are over-represented in patients with Hirschsprung disease and may represent loci modifying phenotypic expression"],"prefix":"10.1136","volume":"36","author":[{"given":"Salud","family":"Borrego","sequence":"first","affiliation":[{"name":"aUnidad de Gen\u00e9tica M\u00e9dica y Diagn\u00f3stico Prenatal, Hospitales Universitarios Virgen del Roc\u00edo, Avenida Manuel Siurot s\/n, 41013 Sevilla, Spain, \n\nbCirug\u00eda Infantil, Hospitales Universitarios Virgen del Roc\u00edo, Sevilla, Spain, \n\ncClinical Cancer Genetics and Human Cancer Genetics Programs, Ohio State University Comprehensive Cancer Center, 420 W 12th Avenue, Suite 690, Columbus, OH 43210, USA, \n\ndCRC Human Cancer Genetics Research Group, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Eugenia","family":"S\u00e1ez","sequence":"additional","affiliation":[{"name":"aUnidad de Gen\u00e9tica M\u00e9dica y Diagn\u00f3stico Prenatal, Hospitales Universitarios Virgen del Roc\u00edo, Avenida Manuel Siurot s\/n, 41013 Sevilla, Spain, \n\nbCirug\u00eda Infantil, Hospitales Universitarios Virgen del Roc\u00edo, Sevilla, Spain, \n\ncClinical Cancer Genetics and Human Cancer Genetics Programs, Ohio State University Comprehensive Cancer Center, 420 W 12th Avenue, Suite 690, Columbus, OH 43210, USA, \n\ndCRC Human Cancer Genetics Research Group, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agust\u00edn","family":"Ruiz","sequence":"additional","affiliation":[{"name":"aUnidad de Gen\u00e9tica M\u00e9dica y Diagn\u00f3stico Prenatal, Hospitales Universitarios Virgen del Roc\u00edo, Avenida Manuel Siurot s\/n, 41013 Sevilla, Spain, \n\nbCirug\u00eda Infantil, Hospitales Universitarios Virgen del Roc\u00edo, Sevilla, Spain, \n\ncClinical Cancer Genetics and Human Cancer Genetics Programs, Ohio State University Comprehensive Cancer Center, 420 W 12th Avenue, Suite 690, Columbus, OH 43210, USA, \n\ndCRC Human Cancer Genetics Research Group, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Gimm","sequence":"additional","affiliation":[{"name":"aUnidad de Gen\u00e9tica M\u00e9dica y Diagn\u00f3stico Prenatal, Hospitales Universitarios Virgen del Roc\u00edo, Avenida Manuel Siurot s\/n, 41013 Sevilla, Spain, \n\nbCirug\u00eda Infantil, Hospitales Universitarios Virgen del Roc\u00edo, Sevilla, Spain, \n\ncClinical Cancer Genetics and Human Cancer Genetics Programs, Ohio State University Comprehensive Cancer Center, 420 W 12th Avenue, Suite 690, Columbus, OH 43210, USA, \n\ndCRC Human Cancer Genetics Research Group, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"L\u00f3pez-Alonso","sequence":"additional","affiliation":[{"name":"aUnidad de Gen\u00e9tica M\u00e9dica y Diagn\u00f3stico Prenatal, Hospitales Universitarios Virgen del Roc\u00edo, Avenida Manuel Siurot s\/n, 41013 Sevilla, Spain, \n\nbCirug\u00eda Infantil, Hospitales Universitarios Virgen del Roc\u00edo, Sevilla, Spain, \n\ncClinical Cancer Genetics and Human Cancer Genetics Programs, Ohio State University Comprehensive Cancer Center, 420 W 12th Avenue, Suite 690, Columbus, OH 43210, USA, \n\ndCRC Human Cancer Genetics Research Group, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Anti\u00f1olo","sequence":"additional","affiliation":[{"name":"aUnidad de Gen\u00e9tica M\u00e9dica y Diagn\u00f3stico Prenatal, Hospitales Universitarios Virgen del Roc\u00edo, Avenida Manuel Siurot s\/n, 41013 Sevilla, Spain, \n\nbCirug\u00eda Infantil, Hospitales Universitarios Virgen del Roc\u00edo, Sevilla, Spain, \n\ncClinical Cancer Genetics and Human Cancer Genetics Programs, Ohio State University Comprehensive Cancer Center, 420 W 12th Avenue, Suite 690, Columbus, OH 43210, USA, \n\ndCRC Human Cancer Genetics Research Group, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charis","family":"Eng","sequence":"additional","affiliation":[{"name":"aUnidad de Gen\u00e9tica M\u00e9dica y Diagn\u00f3stico Prenatal, Hospitales Universitarios Virgen del Roc\u00edo, Avenida Manuel Siurot s\/n, 41013 Sevilla, Spain, \n\nbCirug\u00eda Infantil, Hospitales Universitarios Virgen del Roc\u00edo, Sevilla, Spain, \n\ncClinical Cancer Genetics and Human Cancer Genetics Programs, Ohio State University Comprehensive Cancer Center, 420 W 12th Avenue, Suite 690, Columbus, OH 43210, USA, \n\ndCRC Human Cancer Genetics Research Group, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1999,10,1]]},"reference":[{"key":"2025100521005702000_36.10.771.1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1056\/NEJM196701192760303","article-title":"The genetics of Hirschsprung\u2019s disease.","volume":"276","author":"Passarge","year":"1967","journal-title":"N Engl J Med"},{"key":"2025100521005702000_36.10.771.2","first-page":"568","article-title":"A genetic study of Hirschsprung disease.","volume":"46","author":"Badner","year":"1990","journal-title":"Am J Hum 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