{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:56:56Z","timestamp":1792738616269,"version":"4.5.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"33","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,8,18]]},"abstract":"<jats:p>\n                    Hirschsprung disease (HSCR) is a common, multigenic neurocristopathy characterized by incomplete innervation along a variable length of the gut. The pivotal gene in isolated HSCR cases, either sporadic or familial, is\n                    <jats:italic>RET<\/jats:italic>\n                    . HSCR also presents in various syndromes, including Shah\u2013Waardenburg syndrome (WS), Down (DS), and Bardet\u2013Biedl (BBS). Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory\n                    <jats:italic>RET<\/jats:italic>\n                    elements, whose functionality is tested in physiologically relevant assays. Our data suggest that BBS mutations can potentiate HSCR predisposing\n                    <jats:italic>RET<\/jats:italic>\n                    alleles, which by themselves are insufficient to cause disease. We also demonstrate that these genes interact genetically in vivo to modulate gut innervation, and that this interaction likely occurs through complementary, yet independent, pathways that converge on the same biological process.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0901219106","type":"journal-article","created":{"date-parts":[[2009,7,31]],"date-time":"2009-07-31T21:31:49Z","timestamp":1249075909000},"page":"13921-13926","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":52,"title":["Epistasis between\n                    <i>RET<\/i>\n                    and\n                    <i>BBS<\/i>\n                    mutations modulates enteric innervation and causes syndromic Hirschsprung disease"],"prefix":"10.1073","volume":"106","author":[{"given":"Lo\u00efc","family":"de Pontual","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U781, 6 Service de G\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants-Malades, AP-HP, 75743 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norann A.","family":"Zaghloul","sequence":"additional","affiliation":[{"name":"McKusick\u2013Nathans Institute of Genetic Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Thomas","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U781, 6 Service de G\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants-Malades, AP-HP, 75743 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica E.","family":"Davis","sequence":"additional","affiliation":[{"name":"McKusick\u2013Nathans Institute of Genetic Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Mcgaughey","sequence":"additional","affiliation":[{"name":"McKusick\u2013Nathans Institute of Genetic Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Dollfus","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital de Haute-Pierre, F-67098 Strasbourg, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Baumann","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital Robert Debr\u00e9, 75935 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seneca L.","family":"Bessling","sequence":"additional","affiliation":[{"name":"McKusick\u2013Nathans Institute of Genetic Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candice","family":"Babarit","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U781, 6 Service de G\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants-Malades, AP-HP, 75743 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pelet","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U781, 6 Service de G\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants-Malades, AP-HP, 75743 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Gascue","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Montevideo, CP11400 Montevideo, Uruguay;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Beales","sequence":"additional","affiliation":[{"name":"Molecular Medicine Unit, Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Munnich","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U781, 6 Service de G\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants-Malades, AP-HP, 75743 Paris, France;"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes, 75270 Paris, France;"},{"name":"Molecular Medicine Unit, Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislas","family":"Lyonnet","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U781, 6 Service de G\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants-Malades, AP-HP, 75743 Paris, France;"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes, 75270 Paris, France;"},{"name":"Molecular Medicine Unit, Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Etchevers","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U781, 6 Service de G\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants-Malades, AP-HP, 75743 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Attie-Bitach","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U781, 6 Service de G\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants-Malades, AP-HP, 75743 Paris, France;"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes, 75270 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"Badano","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Montevideo, CP11400 Montevideo, Uruguay;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"McCallion","sequence":"additional","affiliation":[{"name":"McKusick\u2013Nathans Institute of Genetic Medicine,"},{"name":"Department of Molecular and Comparative Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Katsanis","sequence":"additional","affiliation":[{"name":"McKusick\u2013Nathans Institute of Genetic Medicine,"},{"name":"Department of Molecular Biology and Genetics, and"},{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205;"},{"name":"Center for Human Disease Modeling, Department of Cell Biology, Duke University Medical Center, Durham, NC 27708"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Amiel","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U781, 6 Service de G\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants-Malades, AP-HP, 75743 Paris, France;"},{"name":"Molecular Medicine Unit, Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; 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The Metabolic and Molecular Bases of Inherited Disease, eds CR Scriver, AR Beaudet, D Valle, W Sly (McGraw-Hill, 8th Ed., New York, Chap 251. (2007).","edition":"8"},{"key":"e_1_3_3_21_2","volume-title":"Inborn Errors of Development","author":"McCallion AS","year":"2008","unstructured":"AS McCallion, RET, Hirschsprung disease and multiple endocrine neoplasia type 2. 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