{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:39:44Z","timestamp":1790109584889,"version":"4.0.1"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071685"],"award-info":[{"award-number":["82071685"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Research Pilot Project of Tongji Hospital","award":["2019YBKY026"],"award-info":[{"award-number":["2019YBKY026"]}]},{"name":"Provincial Key Research and Development Program","award":["2020BCB008"],"award-info":[{"award-number":["2020BCB008"]}]},{"name":"Science and Technology Innovation Base Platform","award":["2020DCD006"],"award-info":[{"award-number":["2020DCD006"]}]},{"name":"Project of Shenzhen San Ming","award":["SZSM201812055"],"award-info":[{"award-number":["SZSM201812055"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["World J Pediatr"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Hirschsprung\u2019s disease (HSCR) is one of the most common congenital digestive tract malformations and can cause stubborn constipation or gastrointestinal obstruction after birth, causing great physical and mental pain to patients and their families. Studies have shown that more than 20 genes are involved in HSCR, and most cases of HSCR are sporadic. However, the overall rate of familial recurrence in 4331 cases of HSCR is about 7.6%. Furthermore, familial HSCR patients show incomplete dominance. We still do not know the penetrance and genetic characteristics of these known risk genes due to the rarity of HSCR families.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>To find published references, we used the title\/abstract terms \u201cHirschsprung\u201d and \u201cfamilial\u201d in the PubMed database and the MeSH terms \u201cHirschsprung\u201d and \u201cfamilial\u201d in Web of Science. Finally, we summarized 129 HSCR families over the last 40\u00a0years.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The male-to-female ratio and the percentage of short segment-HSCR in familial HSCR are much lower than in sporadic HSCR. The primary gene factors in the syndromic families are ret proto-oncogene\u00a0(<jats:italic>RET<\/jats:italic>) and endothelin B receptor gene\u00a0(<jats:italic>EDNRB<\/jats:italic>). Most families show incomplete dominance and are relevant to <jats:italic>RET<\/jats:italic>, and the <jats:italic>RET<\/jats:italic> mutation has 56% penetrance in familial HSCR. When one of the parents is a <jats:italic>RET<\/jats:italic> mutation carrier in an HSCR family, the offspring\u2019s recurrence risk is 28%, and the incidence of the offspring does not depend on whether the parent suffers from HSCR.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our findings will help HSCR patients obtain better genetic counseling, calculate the risk of recurrence, and provide new insights for future pedigree studies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12519-023-00686-x","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T12:03:12Z","timestamp":1677672192000},"page":"644-651","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Comprehensive characterization of the genetic landscape of familial Hirschsprung\u2019s disease"],"prefix":"10.1007","volume":"19","author":[{"given":"Jun","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Wen","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Si","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Yi","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-Jian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Dan","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yao","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Xiong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,1]]},"reference":[{"key":"686_CR1","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1186\/s13023-020-01362-3","volume":"15","author":"K Kyrklund","year":"2020","unstructured":"Kyrklund K, Sloots CEJ, de Blaauw I, Bj\u00f8rnland K, Rolle U, Cavalieri D, et al. ERNICA guidelines for the management of rectosigmoid Hirschsprung\u2019s disease. Orphanet J Rare Dis. 2020;15:164.","journal-title":"Orphanet J Rare Dis"},{"key":"686_CR2","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/367377a0","volume":"367","author":"G Romeo","year":"1994","unstructured":"Romeo G, Ronchetto P, Luo Y, Barone V, Seri M, Ceccherini I, et al. Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung\u2019s disease. Nature. 1994;367:377\u20138.","journal-title":"Nature"},{"key":"686_CR3","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1016\/0092-8674(94)90017-5","volume":"79","author":"K Hosoda","year":"1994","unstructured":"Hosoda K, Hammer RE, Richardson JA, Baynash AG, Cheung JC, Giaid A, et al. Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. Cell. 1994;79:1267\u201376.","journal-title":"Cell"},{"key":"686_CR4","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1136\/gut.52.4.563","volume":"52","author":"M Garcia-Barcel\u00f3","year":"2003","unstructured":"Garcia-Barcel\u00f3 M, Sham MH, Lui VC, Chen BL, Ott J, Tam PK. Association study of PHOX2B as a candidate gene for Hirschsprung\u2019s disease. Gut. 2003;52:563\u20137.","journal-title":"Gut"},{"key":"686_CR5","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1056\/NEJMoa1706594","volume":"380","author":"JM Tilghman","year":"2019","unstructured":"Tilghman JM, Ling AY, Turner TN, Sosa MX, Krumm N, Chatterjee S, et al. Molecular genetic anatomy and risk profile of Hirschsprung\u2019s disease. N Engl J Med. 2019;380:1421\u201332.","journal-title":"N Engl J Med"},{"key":"686_CR6","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1073\/pnas.97.1.268","volume":"97","author":"S Bolk","year":"2000","unstructured":"Bolk S, Pelet A, Hofstra RM, Angrist M, Salomon R, Croaker D, et al. A human model for multigenic inheritance: phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus. Proc Natl Acad Sci U S A. 2000;97:268\u201373.","journal-title":"Proc Natl Acad Sci USA"},{"key":"686_CR7","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1111\/j.1399-0004.1994.tb04147.x","volume":"45","author":"MB Russell","year":"1994","unstructured":"Russell MB, Russell CA, Fenger K, Niebuhr E. Familial occurrence of Hirschsprung\u2019s disease. Clin Genet. 1994;45:231\u20135.","journal-title":"Clin Genet"},{"key":"686_CR8","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1136\/jmg.31.8.602","volume":"31","author":"P Edery","year":"1994","unstructured":"Edery P, Pelet A, Mulligan LM, Abel L, Atti\u00e9 T, Dow E, et al. Long segment and short segment familial Hirschsprung\u2019s disease: variable clinical expression at the RET locus. J Med Genet. 1994;31:602\u20136.","journal-title":"J Med Genet"},{"key":"686_CR9","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1007\/s00383-015-3730-z","volume":"31","author":"D Mc Laughlin","year":"2015","unstructured":"Mc Laughlin D, Puri P. Familial Hirschsprung\u2019s disease: a systematic review. Pediatr Surg Int. 2015;31:695\u2013700.","journal-title":"Pediatr Surg Int"},{"key":"686_CR10","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1007\/s00383-017-4134-z","volume":"33","author":"T Kawano","year":"2017","unstructured":"Kawano T, Hosomichi K, Inoue I, Shimono R, Onishi S, Nakame K, et al. Identification of a novel variant of the RET proto-oncogene in a novel family with Hirschsprung\u2019s disease. Pediatr Surg Int. 2017;33:1041\u20136.","journal-title":"Pediatr Surg Int"},{"key":"686_CR11","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.jpedsurg.2013.10.027","volume":"49","author":"AL Granstr\u00f6m","year":"2014","unstructured":"Granstr\u00f6m AL, Markljung E, Fink K, Nordenskj\u00f6ld E, Nilsson D, Wester T, et al. A novel stop mutation in the EDNRB gene in a family with Hirschsprung\u2019s disease associated with multiple sclerosis. J Pediatr Surg. 2014;49:622\u20135.","journal-title":"J Pediatr Surg"},{"key":"686_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1528","volume":"8","author":"NP Pace","year":"2020","unstructured":"Pace NP, Pace Bardon M, Borg I. A respiratory\/Hirschsprung phenotype in a three-generation family associated with a novel pathogenic PHOX2B splice donor mutation. Mol Genet Genomic Med. 2020;8:e1528.","journal-title":"Mol Genet Genomic Med"},{"key":"686_CR13","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1093\/hmg\/4.8.1381","volume":"4","author":"T Atti\u00e9","year":"1995","unstructured":"Atti\u00e9 T, Pelet A, Edery P, Eng C, Mulligan LM, Amiel J, et al. Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung disease. Hum Mol Genet. 1995;4:1381\u20136.","journal-title":"Hum Mol Genet"},{"key":"686_CR14","doi-asserted-by":"publisher","first-page":"e145837","DOI":"10.1172\/JCI145837","volume":"131","author":"TL Le","year":"2021","unstructured":"Le TL, Galmiche L, Levy J, Suwannarat P, Hellebrekers DM, Morarach K, et al. Dysregulation of the NRG1\/ERBB pathway causes a developmental disorder with gastrointestinal dysmotility in humans. J Clin Invest. 2021;131:e145837.","journal-title":"J Clin Invest"},{"key":"686_CR15","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1002\/ajmg.a.38218","volume":"173","author":"RC Lombardo","year":"2017","unstructured":"Lombardo RC, Kramer E, Cnota JF, Sawnani H, Hopkin RJ. Variable phenotype in a novel mutation in PHOX2B. Am J Med Genet A. 2017;173:1705\u20139.","journal-title":"Am J Med Genet A"},{"key":"686_CR16","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1007\/s00439-020-02247-y","volume":"140","author":"Q Jiang","year":"2021","unstructured":"Jiang Q, Wang Y, Gao Y, Wang H, Zhang Z, Li Q, et al. RET compound inheritance in Chinese patients with Hirschsprung disease: lack of penetrance from insufficient gene dysfunction. Hum Genet. 2021;140:813\u201325.","journal-title":"Hum Genet"},{"key":"686_CR17","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1186\/s13023-019-1194-2","volume":"14","author":"Q Jiang","year":"2019","unstructured":"Jiang Q, Wang Y, Li Q, Zhang Z, Xiao P, Wang H, et al. Sequence characterization of RET in 117 Chinese Hirschsprung disease families identifies a large burden of de novo and parental mosaic mutations. Orphanet J Rare Dis. 2019;14:237.","journal-title":"Orphanet J Rare Dis"},{"key":"686_CR18","doi-asserted-by":"publisher","first-page":"e13665","DOI":"10.1111\/nmo.13665","volume":"31","author":"W Yang","year":"2019","unstructured":"Yang W, Chen SC, Lai JY, Ming YC, Chen JC, Chen PL. Distinctive genetic variation of long-segment Hirschsprung\u2019s disease in Taiwan. Neurogastroenterol Motil. 2019;31:e13665.","journal-title":"Neurogastroenterol Motil"},{"key":"686_CR19","doi-asserted-by":"publisher","first-page":"752","DOI":"10.3389\/fgene.2018.00752","volume":"9","author":"W Wu","year":"2018","unstructured":"Wu W, Lu L, Xu W, Liu J, Sun J, Zheng L, et al. Whole exome sequencing identifies a novel pathogenic RET variant in Hirschsprung disease. Front Genet. 2018;9:752.","journal-title":"Front Genet"},{"key":"686_CR20","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.gene.2018.02.054","volume":"658","author":"Q Shen","year":"2018","unstructured":"Shen Q, Zhang H, Su Y, Wen Z, Zhu Z, Chen G, et al. Identification of two novel PCDHA9 mutations associated with Hirschsprung\u2019s disease. Gene. 2018;658:96\u2013104.","journal-title":"Gene"},{"key":"686_CR21","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1053\/j.gastro.2018.03.034","volume":"155","author":"Y Sribudiani","year":"2018","unstructured":"Sribudiani Y, Chauhan RK, Alves MM, Petrova L, Brosens E, Harrison C, et al. Identification of variants in RET and IHH pathway members in a large family with history of Hirschsprung disease. Gastroenterology. 2018;155:118\u201329.e6.","journal-title":"Gastroenterology"},{"key":"686_CR22","doi-asserted-by":"publisher","first-page":"16473","DOI":"10.1038\/srep16473","volume":"5","author":"B Luz\u00f3n-Toro","year":"2015","unstructured":"Luz\u00f3n-Toro B, Gui H, Ruiz-Ferrer M, Sze-Man Tang C, Fern\u00e1ndez RM, Sham PC, et al. Exome sequencing reveals a high genetic heterogeneity on familial Hirschsprung disease. Sci Rep. 2015;5:16473.","journal-title":"Sci Rep"},{"key":"686_CR23","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1159\/000371590","volume":"6","author":"Y Doubaj","year":"2015","unstructured":"Doubaj Y, Pingault V, Elalaoui SC, Ratbi I, Azouz M, Zerhouni H, et al. A novel mutation in the endothelin B receptor gene in a moroccan family with shah-waardenburg syndrome. Mol Syndromol. 2015;6:44\u20139.","journal-title":"Mol Syndromol"},{"key":"686_CR24","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1272\/jnms.81.64","volume":"81","author":"T Igarashi","year":"2014","unstructured":"Igarashi T, Okamura R, Jikuzono T, Uchino S, Sugitani I, Shimizu K. An extended family with familial medullary thyroid carcinoma and Hirschsprung\u2019s disease. J Nippon Med Sch. 2014;81:64\u20139.","journal-title":"J Nippon Med Sch"},{"key":"686_CR25","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/1752-1947-7-117","volume":"7","author":"E Bygarski","year":"2013","unstructured":"Bygarski E, Paterson M, Lemire EG. Extreme intra-familial variability of congenital central hypoventilation syndrome: a case series. J Med Case Rep. 2013;7:117.","journal-title":"J Med Case Rep"},{"key":"686_CR26","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1136\/jmg.32.7.531","volume":"32","author":"G Van Camp","year":"1995","unstructured":"Van Camp G, Van Thienen MN, Handig I, Van Roy B, Rao VS, Milunsky A, et al. Chromosome 13q deletion with Waardenburg syndrome: further evidence for a gene involved in neural crest function on 13q. J Med Genet. 1995;32:531\u20136.","journal-title":"J Med Genet"},{"key":"686_CR27","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1136\/jmg.2009.067819","volume":"46","author":"A S\u00e1nchez-Mej\u00edas","year":"2009","unstructured":"S\u00e1nchez-Mej\u00edas A, Fern\u00e1ndez RM, L\u00f3pez-Alonso M, Anti\u00f1olo G, Borrego S. Contribution of RET, NTRK3 and EDN3 to the expression of Hirschsprung disease in a multiplex family. J Med Genet. 2009;46:862\u20134.","journal-title":"J Med Genet"},{"key":"686_CR28","doi-asserted-by":"publisher","first-page":"e66631","DOI":"10.1371\/journal.pone.0066631","volume":"8","author":"L Cui","year":"2013","unstructured":"Cui L, Wong EH, Cheng G, Firmato de Almeida M, So MT, Sham PC, et al. Genetic analyses of a three generation family segregating Hirschsprung disease and iris heterochromia. PLoS One. 2013;8:e66631.","journal-title":"PLoS One"},{"key":"686_CR29","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.jpedsurg.2012.10.061","volume":"48","author":"K Ohno","year":"2013","unstructured":"Ohno K, Nakamura T, Azuma T, Nakaoka T, Takama Y, Hayashi H, et al. Familial Currarino syndrome associated with Hirschsprung disease: two cases of a mother and daughter. J Pediatr Surg. 2013;48:233\u20138.","journal-title":"J Pediatr Surg"},{"key":"686_CR30","doi-asserted-by":"publisher","first-page":"13921","DOI":"10.1073\/pnas.0901219106","volume":"106","author":"L de Pontual","year":"2009","unstructured":"de Pontual L, Zaghloul NA, Thomas S, Davis EE, McGaughey DM, Dollfus H, et al. Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease. Proc Natl Acad Sci U S A. 2009;106:13921\u20136.","journal-title":"Proc Natl Acad Sci USA"},{"key":"686_CR31","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.jpedsurg.2009.10.080","volume":"45","author":"SW Moore","year":"2010","unstructured":"Moore SW, Zaahl M. Familial associations in medullary thyroid carcinoma with Hirschsprung disease: the role of the RET-C620 \u201cJanus\u201d genetic variation. J Pediatr Surg. 2010;45:393\u20136.","journal-title":"J Pediatr Surg"},{"key":"686_CR32","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1016\/j.jpedsurg.2008.02.013","volume":"43","author":"MP Cherian","year":"2008","unstructured":"Cherian MP, Al-Sanna\u2019a NA, Al-Mulhim SI. Hirschsprung\u2019s disease in Arab siblings with Bardet-Biedl syndrome. J Pediatr Surg. 2008;43:1213\u20137.","journal-title":"J Pediatr Surg"},{"key":"686_CR33","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/sj.ejhg.5201733","volume":"15","author":"L Basel-Vanagaite","year":"2007","unstructured":"Basel-Vanagaite L, Pelet A, Steiner Z, Munnich A, Rozenbach Y, Shohat M, et al. Allele dosage-dependent penetrance of RET proto-oncogene in an Israeli-Arab inbred family segregating Hirschsprung disease. Eur J Hum Genet. 2007;15:242\u20135.","journal-title":"Eur J Hum Genet"},{"key":"686_CR34","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.jpedsurg.2007.10.021","volume":"43","author":"SW Moore","year":"2008","unstructured":"Moore SW, Zaahl MG. A review of genetic mutation in familial Hirschsprung\u2019s disease in South Africa: towards genetic counseling. J Pediatr Surg. 2008;43:325\u20139.","journal-title":"J Pediatr Surg"},{"key":"686_CR35","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.jpedsurg.2007.09.043","volume":"43","author":"EA Fialkowski","year":"2008","unstructured":"Fialkowski EA, DeBenedetti MK, Moley JF, Bachrach B. RET proto-oncogene testing in infants presenting with Hirschsprung disease identifies 2 new multiple endocrine neoplasia 2A kindreds. J Pediatr Surg. 2008;43:188\u201390.","journal-title":"J Pediatr Surg"},{"key":"686_CR36","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1373\/clinchem.2005.051904","volume":"51","author":"VC Lui","year":"2005","unstructured":"Lui VC, Leon TY, Garcia-Barcel\u00f3 MM, Ganster RW, Chen BL, Hutson JM, et al. Novel RET mutation produces a truncated RET receptor lacking the intracellular signaling domain in a 3-generation family with Hirschsprung disease. Clin Chem. 2005;51:1552\u20134.","journal-title":"Clin Chem"},{"key":"686_CR37","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1111\/j.1399-0004.2004.00312.x","volume":"66","author":"DM Gilchrist","year":"2004","unstructured":"Gilchrist DM, Morrish DW, Bridge PJ, Brown JL. Cost analysis of DNA-based testing in a large Canadian family with multiple endocrine neoplasia type 2. Clin Genet. 2004;66:349\u201352.","journal-title":"Clin Genet"},{"key":"686_CR38","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1002\/humu.10273","volume":"22","author":"RM Fern\u00e1ndez","year":"2003","unstructured":"Fern\u00e1ndez RM, Anti\u00f1olo G, Eng C, Borrego S. The RET C620S mutation causes multiple endocrine neoplasia type 2A (MEN2A) but not Hirschsprung disease (HSCR) in a family cosegregating both phenotypes. Hum Mutat. 2003;22:412\u20135.","journal-title":"Hum Mutat"},{"key":"686_CR39","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1055\/s-2003-41270","volume":"13","author":"G Fitze","year":"2003","unstructured":"Fitze G, Cramer J, Serra A, Schreiber M, Roesner D, Schackert HK. Within-gene interaction between c.135 G\/A genotypes and RET proto-oncogene germline mutations in HSCR families. Eur J Pediatr Surg. 2003;13:152\u20137.","journal-title":"Eur J Pediatr Surg"},{"key":"686_CR40","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/1096-8628(20000904)94:1<19::AID-AJMG5>3.0.CO;2-K","volume":"94","author":"M Munnes","year":"2000","unstructured":"Munnes M, Fanaei S, Schmitz B, Muiznieks I, Holschneider AM, Doerfler W. Familial form of hirschsprung disease: nucleotide sequence studies reveal point mutations in the RET proto-oncogene in two of six families but not in other candidate genes. Am J Med Genet. 2000;94:19\u201327.","journal-title":"Am J Med Genet"},{"key":"686_CR41","unstructured":"Brooks AS, Breuning MH, Osinga J, vd Smagt JJ, Catsman CE, Buys CH, et al. A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome). J Med Genet. 1999;36:485\u20139."},{"key":"686_CR42","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1093\/hmg\/7.1.129","volume":"7","author":"RA Decker","year":"1998","unstructured":"Decker RA, Peacock ML, Watson P. Hirschsprung disease in MEN 2A: increased spectrum of RET exon 10 genotypes and strong genotype-phenotype correlation. Hum Mol Genet. 1998;7:129\u201334.","journal-title":"Hum Mol Genet"},{"key":"686_CR43","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1046\/j.1365-2796.1998.00332.x","volume":"243","author":"G Romeo","year":"1998","unstructured":"Romeo G, Ceccherini I, Celli J, Priolo M, Betsos N, Bonardi G, et al. Association of multiple endocrine neoplasia type 2 and Hirschsprung disease. J Intern Med. 1998;243:515\u201320.","journal-title":"J Intern Med"},{"key":"686_CR44","first-page":"3361","volume":"83","author":"S Borrego","year":"1998","unstructured":"Borrego S, Eng C, S\u00e1nchez B, S\u00e1ez ME, Navarro E, Anti\u00f1olo G. Molecular analysis of the ret and GDNF genes in a family with multiple endocrine neoplasia type 2A and Hirschsprung disease. J Clin Endocrinol Metab. 1998;83:3361\u20134.","journal-title":"J Clin Endocrinol Metab"},{"key":"686_CR45","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1002\/(SICI)1098-1004(1997)10:2<155::AID-HUMU7>3.0.CO;2-J","volume":"10","author":"H Peretz","year":"1997","unstructured":"Peretz H, Luboshitsky R, Baron E, Biton A, Gershoni R, Usher S, et al. Cys 618 Arg mutation in the RET proto-oncogene associated with familial medullary thyroid carcinoma and maternally transmitted Hirschsprung\u2019s disease suggesting a role for imprinting. Hum Mutat. 1997;10:155\u20139.","journal-title":"Hum Mutat"},{"key":"686_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/(SICI)1096-911X(199701)28:1<1::AID-MPO1>3.0.CO;2-P","volume":"28","author":"JM Maris","year":"1997","unstructured":"Maris JM, Chatten J, Meadows AT, Biegel JA, Brodeur GM. Familial neuroblastoma: a three-generation pedigree and a further association with Hirschsprung disease. Med Pediatr Oncol. 1997;28:1\u20135.","journal-title":"Med Pediatr Oncol"},{"key":"686_CR47","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/ng1196-345","volume":"14","author":"R Salomon","year":"1996","unstructured":"Salomon R, Atti\u00e9 T, Pelet A, Bidaud C, Eng C, Amiel J, et al. Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease. Nat Genet. 1996;14:345\u20137.","journal-title":"Nat Genet"},{"key":"686_CR48","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1136\/jmg.32.4.312","volume":"32","author":"T Atti\u00e9","year":"1995","unstructured":"Atti\u00e9 T, Till M, Pelet A, Edery P, Bonnet JP, Munnich A, et al. Exclusion of RET and Pax 3 loci in Waardenburg-Hirschsprung disease. J Med Genet. 1995;32:312\u20133.","journal-title":"J Med Genet"},{"key":"686_CR49","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/ng0496-445","volume":"12","author":"RM Hofstra","year":"1996","unstructured":"Hofstra RM, Osinga J, Tan-Sindhunata G, Wu Y, Kamsteeg EJ, Stulp RP, et al. A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome). Nat Genet. 1996;12:445\u20137.","journal-title":"Nat Genet"},{"key":"686_CR50","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1093\/hmg\/4.5.821","volume":"4","author":"M Angrist","year":"1995","unstructured":"Angrist M, Bolk S, Thiel B, Puffenberger EG, Hofstra RM, Buys CH, et al. Mutation analysis of the RET receptor tyrosine kinase in Hirschsprung disease. Hum Mol Genet. 1995;4:821\u201330.","journal-title":"Hum Mol Genet"},{"key":"686_CR51","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1111\/j.1399-0004.1995.tb03946.x","volume":"47","author":"JW Pierpont","year":"1995","unstructured":"Pierpont JW, St Jacques D, Seaver LH, Erickson RP. A family with unusual Waardenburg syndrome type I (WSI), cleft lip (palate), and Hirschsprung disease is not linked to PAX 3. Clin Genet. 1995;47:139\u201343.","journal-title":"Clin Genet"},{"key":"686_CR52","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1093\/hmg\/3.8.1439","volume":"3","author":"T Attie","year":"1994","unstructured":"Attie T, Pelet A, Sarda P, Eng C, Edery P, Mulligan LM, et al. A 7 bp deletion of the RET proto-oncogene in familial Hirschsprung\u2019s disease. Hum Mol Genet. 1994;3:1439\u201340.","journal-title":"Hum Mol Genet"},{"key":"686_CR53","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1055\/s-2008-1066521","volume":"6","author":"JP Bonnet","year":"1996","unstructured":"Bonnet JP, Till M, Edery P, Attie T, Lyonnet S. Waardenburg-Hirschsprung disease in two sisters: a possible clue to the genetics of this association? Eur J Pediatr Surg. 1996;6:245\u20138.","journal-title":"Eur J Pediatr Surg"},{"key":"686_CR54","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1093\/hmg\/3.12.2163","volume":"3","author":"LM Mulligan","year":"1994","unstructured":"Mulligan LM, Eng C, Atti\u00e9 T, Lyonnet S, Marsh DJ, Hyland VJ, et al. Diverse phenotypes associated with exon 10 mutations of the RET proto-oncogene. Hum Mol Genet. 1994;3:2163\u20137.","journal-title":"Hum Mol Genet"},{"key":"686_CR55","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/ajmg.1320530116","volume":"53","author":"E Dow","year":"1994","unstructured":"Dow E, Cross S, Wolgemuth DJ, Lyonnet S, Mulligan LM, Mascari M, et al. Second locus for Hirschsprung disease\/Waardenburg syndrome in a large Mennonite kindred. Am J Med Genet. 1994;53:75\u201380.","journal-title":"Am J Med Genet"},{"key":"686_CR56","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/ng0893-351","volume":"4","author":"M Angrist","year":"1993","unstructured":"Angrist M, Kauffman E, Slaugenhaupt SA, Matise TC, Puffenberger EG, Washington SS, et al. A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10. Nat Genet. 1993;4:351\u20136.","journal-title":"Nat Genet"},{"key":"686_CR57","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1093\/hmg\/2.11.1803","volume":"2","author":"Y Luo","year":"1993","unstructured":"Luo Y, Ceccherini I, Pasini B, Matera I, Bicocchi MP, Barone V, et al. Close linkage with the RET protooncogene and boundaries of deletion mutations in autosomal dominant Hirschsprung disease. Hum Mol Genet. 1993;2:1803\u20138.","journal-title":"Hum Mol Genet"},{"key":"686_CR58","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/0022-3468(91)90714-5","volume":"26","author":"VA Stannard","year":"1991","unstructured":"Stannard VA, Fowler C, Robinson L, Besner G, Glick PL, Allen JE, et al. Familial Hirschsprung\u2019s disease: report of autosomal dominant and probable recessive X-linked kindreds. J Pediatr Surg. 1991;26:591\u20134.","journal-title":"J Pediatr Surg"},{"key":"686_CR59","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/0022-3468(90)90077-M","volume":"25","author":"M Schiller","year":"1990","unstructured":"Schiller M, Levy P, Shawa RA, Abu-Dalu K, Gorenstein A, Katz S. Familial Hirschsprung\u2019s disease-a report of 22 affected siblings in four families. J Pediatr Surg. 1990;25:322\u20135.","journal-title":"J Pediatr Surg"},{"key":"686_CR60","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1097\/00005176-198212000-00027","volume":"1","author":"M Verdy","year":"1982","unstructured":"Verdy M, Weber AM, Roy CC, Morin CL, Cadotte M, Brochu P. Hirschsprung\u2019s disease in a family with multiple endocrine neoplasia type 2. J Pediatr Gastroenterol Nutr. 1982;1:603\u20137.","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"686_CR61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/jmg.2007.053959","volume":"45","author":"J Amiel","year":"2008","unstructured":"Amiel J, Sproat-Emison E, Garcia-Barcelo M, Lantieri F, Burzynski G, Borrego S, et al. Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet. 2008;45:1\u201314.","journal-title":"J Med Genet"}],"container-title":["World Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12519-023-00686-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12519-023-00686-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12519-023-00686-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,11]],"date-time":"2023-06-11T16:02:14Z","timestamp":1686499334000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12519-023-00686-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,1]]},"references-count":61,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["686"],"URL":"https:\/\/doi.org\/10.1007\/s12519-023-00686-x","relation":{},"ISSN":["1708-8569","1867-0687"],"issn-type":[{"value":"1708-8569","type":"print"},{"value":"1867-0687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,1]]},"assertion":[{"value":"4 October 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not needed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. Author Jie-Xiong Feng is a member of the Editorial Board for <i>World Journal of Pediatrics<\/i>. The paper was handled by the other Editor and has undergone rigorous peer review process. Author Jie-Xiong Feng was not involved in the journal's review of, or decisions related to, this manuscript.\u00a0The authors have no conflict of interest to declare.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}