{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T07:51:19Z","timestamp":1794124279352,"version":"4.8.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2015,7,12]],"date-time":"2015-07-12T00:00:00Z","timestamp":1436659200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Surg Int"],"published-print":{"date-parts":[[2015,8]]},"DOI":"10.1007\/s00383-015-3731-y","type":"journal-article","created":{"date-parts":[[2015,7,11]],"date-time":"2015-07-11T06:26:42Z","timestamp":1436596002000},"page":"701-710","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["RET gene is a major risk factor for Hirschsprung\u2019s disease: a meta-analysis"],"prefix":"10.1007","volume":"31","author":[{"given":"C.","family":"Tomuschat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Puri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,7,12]]},"reference":[{"key":"3731_CR1","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nrn2137","volume":"8","author":"TA Heanue","year":"2007","unstructured":"Heanue TA, Pachnis V (2007) Enteric nervous system development and Hirschsprung\u2019s disease: advances in genetic and stem cell studies. Nat Rev Neurosci 8:466\u2013479","journal-title":"Nat Rev Neurosci"},{"key":"3731_CR2","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3109\/07853899808999386","volume":"30","author":"K Wartiovaara","year":"1998","unstructured":"Wartiovaara K, Salo M, Sariola H (1998) Hirschsprung\u2019s disease genes and the development of the enteric nervous system. Ann Med 30:66\u201374","journal-title":"Ann Med"},{"key":"3731_CR3","first-page":"1117","volume":"28","author":"S Borrego","year":"2013","unstructured":"Borrego S, Ruiz-Ferrer M, Fernandez RM, Antinolo G (2013) Hirschsprung\u2019s disease as a model of complex genetic etiology. Histol Histopathol 28:1117\u20131136","journal-title":"Histol Histopathol"},{"key":"3731_CR4","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1093\/hmg\/4.8.1381","volume":"4","author":"T Attie","year":"1995","unstructured":"Attie T, Pelet A, Edery P et al (1995) Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung disease. Hum Mol Genet 4:1381\u20131386","journal-title":"Hum Mol Genet"},{"key":"3731_CR5","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1093\/hmg\/4.5.821","volume":"4","author":"M Angrist","year":"1995","unstructured":"Angrist M, Bolk S, Thiel B et al (1995) Mutation analysis of the RET receptor tyrosine kinase in Hirschsprung disease. Hum Mol Genet 4:821\u2013830","journal-title":"Hum Mol Genet"},{"key":"3731_CR6","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s00383-013-3351-3","volume":"29","author":"F Friedmacher","year":"2013","unstructured":"Friedmacher F, Puri P (2013) Classification and diagnostic criteria of variants of Hirschsprung\u2019s disease. Pediatr Surg Int 29:855\u2013872","journal-title":"Pediatr Surg Int"},{"key":"3731_CR7","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1007\/s00383-013-3361-1","volume":"29","author":"F Friedmacher","year":"2013","unstructured":"Friedmacher F, Puri P (2013) Hirschsprung\u2019s disease associated with down syndrome: a meta-analysis of incidence, functional outcomes and mortality. Pediatr Surg Int 29:937\u2013946","journal-title":"Pediatr Surg Int"},{"key":"3731_CR8","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/ng1196-341","volume":"14","author":"M Angrist","year":"1996","unstructured":"Angrist M, Bolk S, Halushka M, Lapchak PA, Chakravarti A (1996) Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient. Nat Genet 14:341\u2013344","journal-title":"Nat Genet"},{"key":"3731_CR9","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/S0896-6273(03)00730-X","volume":"40","author":"A Barlow","year":"2003","unstructured":"Barlow A, de Graaff E, Pachnis V (2003) Enteric nervous system progenitors are coordinately controlled by the G protein-coupled receptor EDNRB and the receptor tyrosine kinase RET. Neuron 40:905\u2013916","journal-title":"Neuron"},{"key":"3731_CR10","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1242\/dev.02375","volume":"133","author":"N Bondurand","year":"2006","unstructured":"Bondurand N, Natarajan D, Barlow A, Thapar N, Pachnis V (2006) Maintenance of mammalian enteric nervous system progenitors by SOX10 and endothelin 3 signalling. Development 133:2075\u20132086","journal-title":"Development"},{"key":"3731_CR11","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/382076a0","volume":"382","author":"MW Moore","year":"1996","unstructured":"Moore MW, Klein RD, Farinas I et al (1996) Renal and neuronal abnormalities in mice lacking GDNF. Nature 382:76\u201379","journal-title":"Nature"},{"key":"3731_CR12","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/1471-2350-12-138","volume":"12","author":"R Nunez-Torres","year":"2011","unstructured":"Nunez-Torres R, Fernandez RM, Acosta MJ et al (2011) Comprehensive analysis of RET common and rare variants in a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events. BMC Med Genet 12:138","journal-title":"BMC Med Genet"},{"key":"3731_CR13","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1097\/01.gim.0000245632.06064.f1","volume":"8","author":"M Ruiz-Ferrer","year":"2006","unstructured":"Ruiz-Ferrer M, Fernandez RM, Antinolo G, Lopez-Alonso M, Eng C, Borrego S (2006) A complex additive model of inheritance for Hirschsprung disease is supported by both RET mutations and predisposing RET haplotypes. Genet Med 8:704\u2013710","journal-title":"Genet Med"},{"key":"3731_CR14","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s00109-010-0714-2","volume":"89","author":"M Ruiz-Ferrer","year":"2011","unstructured":"Ruiz-Ferrer M, Torroglosa A, Luzon-Toro B et al (2011) Novel mutations at RET ligand genes preventing receptor activation are associated to Hirschsprung\u2019s disease. J Mol Med (Berl) 89:471\u2013480","journal-title":"J Mol Med (Berl)"},{"key":"3731_CR15","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/382070a0","volume":"382","author":"MP Sanchez","year":"1996","unstructured":"Sanchez MP, Silos-Santiago I, Frisen J, He B, Lira SA, Barbacid M (1996) Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382:70\u201373","journal-title":"Nature"},{"key":"3731_CR16","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s00383-014-3538-2","volume":"30","author":"D Coyle","year":"2014","unstructured":"Coyle D, Friedmacher F, Puri P (2014) The association between Hirschsprung\u2019s disease and multiple endocrine neoplasia type 2a: a systematic review. Pediatr Surg Int 30:751\u2013756","journal-title":"Pediatr Surg Int"},{"key":"3731_CR17","doi-asserted-by":"crossref","unstructured":"Ibanez CF (2013) Structure and physiology of the RET receptor tyrosine kinase. Cold Spring Harb Perspect Biol 5","DOI":"10.1101\/cshperspect.a009134"},{"key":"3731_CR18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0022-3468(05)80172-1","volume":"25","author":"SM Mahaffey","year":"1990","unstructured":"Mahaffey SM, Martin LW, McAdams AJ, Ryckman FC, Torres M (1990) Multiple endocrine neoplasia type II B with symptoms suggesting Hirschsprung\u2019s disease: a case report. J Pediatr Surg 25:101\u2013103","journal-title":"J Pediatr Surg"},{"key":"3731_CR19","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/367380a0","volume":"367","author":"A Schuchardt","year":"1994","unstructured":"Schuchardt A, D\u2019Agati V, Larsson-Blomberg L, Costantini F, Pachnis V (1994) Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367:380\u2013383","journal-title":"Nature"},{"key":"3731_CR20","doi-asserted-by":"crossref","first-page":"4937","DOI":"10.3748\/wjg.v17.i45.4937","volume":"17","author":"AS Wallace","year":"2011","unstructured":"Wallace AS, Anderson RB (2011) Genetic interactions and modifier genes in Hirschsprung\u2019s disease. World J Gastroenterol 17:4937\u20134944","journal-title":"World J Gastroenterol"},{"key":"3731_CR21","first-page":"568","volume":"46","author":"JA Badner","year":"1990","unstructured":"Badner JA, Sieber WK, Garver KL, Chakravarti A (1990) A genetic study of Hirschsprung disease. Am J Hum Genet 46:568\u2013580","journal-title":"Am J Hum Genet"},{"key":"3731_CR22","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.jpedsurg.2011.11.018","volume":"47","author":"SW Moore","year":"2012","unstructured":"Moore SW, Zaahl MG (2012) Intronic RET gene variants in down syndrome-associated Hirschsprung disease in an African population. J Pediatr Surg 47:299\u2013302","journal-title":"J Pediatr Surg"},{"key":"3731_CR23","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1073\/pnas.0809630105","volume":"106","author":"MM Garcia-Barcelo","year":"2009","unstructured":"Garcia-Barcelo MM, Tang CS, Ngan ES et al (2009) Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung\u2019s disease. Proc Natl Acad Sci USA 106:2694\u20132699","journal-title":"Proc Natl Acad Sci USA"},{"key":"3731_CR24","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/ng998","volume":"32","author":"MM Carrasquillo","year":"2002","unstructured":"Carrasquillo MM, McCallion AS, Puffenberger EG, Kashuk CS, Nouri N, Chakravarti A (2002) Genome-wide association study and mouse model identify interaction between RET and EDNRB pathways in Hirschsprung disease. Nat Genet 32:237\u2013244","journal-title":"Nat Genet"},{"key":"3731_CR25","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/nature03467","volume":"434","author":"ES Emison","year":"2005","unstructured":"Emison ES, McCallion AS, Kashuk CS et al (2005) A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. Nature 434:857\u2013863","journal-title":"Nature"},{"key":"3731_CR26","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.3748\/wjg.v8.i6.1108","volume":"8","author":"JC Li","year":"2002","unstructured":"Li JC, Ding SP, Song Y, Li MJ (2002) Mutation of RET gene in Chinese patients with Hirschsprung\u2019s disease. World J Gastroenterol 8:1108\u20131111","journal-title":"World J Gastroenterol"},{"key":"3731_CR27","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1111\/j.1572-0241.2001.03714.x","volume":"96","author":"T Shimotake","year":"2001","unstructured":"Shimotake T, Go S, Inoue K, Tomiyama H, Iwai N (2001) A homozygous missense mutation in the tyrosine E kinase domain of the RET proto-oncogene in an infant with total intestinal aganglionosis. Am J Gastroenterol 96:1286\u20131291","journal-title":"Am J Gastroenterol"},{"key":"3731_CR28","doi-asserted-by":"crossref","first-page":"4507","DOI":"10.1242\/dev.02616","volume":"133","author":"N Asai","year":"2006","unstructured":"Asai N, Fukuda T, Wu Z et al (2006) Targeted mutation of serine 697 in the Ret tyrosine kinase causes migration defect of enteric neural crest cells. Development 133:4507\u20134516","journal-title":"Development"},{"key":"3731_CR29","doi-asserted-by":"crossref","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 et al (2008) Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet 45:1\u201314","journal-title":"J Med Genet"},{"key":"3731_CR30","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1073\/pnas.0337540100","volume":"100","author":"AS McCallion","year":"2003","unstructured":"McCallion AS, Stames E, Conlon RA, Chakravarti A (2003) Phenotype variation in two-locus mouse models of Hirschsprung disease: tissue-specific interaction between Ret and Ednrb. Proc Natl Acad Sci USA 100:1826\u20131831","journal-title":"Proc Natl Acad Sci USA"},{"key":"3731_CR31","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1159\/000472371","volume":"2","author":"L Yin","year":"1994","unstructured":"Yin L, Barone V, Seri M et al (1994) Heterogeneity and low detection rate of RET mutations in Hirschsprung disease. Eur J Hum Genet 2:272\u2013280","journal-title":"Eur J Hum Genet"},{"key":"3731_CR32","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/367377a0","volume":"367","author":"G Romeo","year":"1994","unstructured":"Romeo G, Ronchetto P, Luo Y et al (1994) Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung\u2019s disease. Nature 367:377\u2013378","journal-title":"Nature"},{"key":"3731_CR33","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/(SICI)1098-1004(1997)9:3<243::AID-HUMU5>3.0.CO;2-8","volume":"9","author":"M Seri","year":"1997","unstructured":"Seri M, Yin L, Barone V et al (1997) Frequency of RET mutations in long- and short-segment Hirschsprung disease. Hum Mutat 9:243\u2013249","journal-title":"Hum Mutat"},{"key":"3731_CR34","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S0022-3468(97)90616-3","volume":"32","author":"T Kusafuka","year":"1997","unstructured":"Kusafuka T, Wang Y, Puri P (1997) Mutation analysis of the RET, the endothelin-B receptor, and the endothelin-3 genes in sporadic cases of Hirschsprung\u2019s disease. J Pediatr Surg 32:501\u2013504","journal-title":"J Pediatr Surg"},{"key":"3731_CR35","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s004390050797","volume":"103","author":"PJ Svensson","year":"1998","unstructured":"Svensson PJ, Anvret M, Molander ML, Nordenskj\u00f6ld A (1998) Phenotypic variation in a family with mutations in two Hirschsprung-related genes (RET and endothelin receptor B). Hum Genet 103:145\u2013148","journal-title":"Hum Genet"},{"issue":"4","key":"3731_CR36","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1086\/302329","volume":"64","author":"A Auricchio","year":"1999","unstructured":"Auricchio A, Griseri P, Carpentieri ML et al (1999) Double heterozygosity for a RET substitution interfering with splicing and an EDNRB missense mutation in Hirschsprung disease. Am J Hum Genet 64(4):1216\u20131221","journal-title":"Am J Hum Genet"},{"key":"3731_CR37","doi-asserted-by":"crossref","unstructured":"Sancandi M, Ceccherini I, Costa M et al (2000) Incidence of RET mutations in patients with Hirschsprung\u2019s disease. J Pediatr Surg 35:139\u2013142; discussion 142-143","DOI":"10.1016\/S0022-3468(00)80031-7"},{"key":"3731_CR38","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/1096-8628(20000814)93:4<278::AID-AJMG5>3.0.CO;2-Q","volume":"93","author":"K Inoue","year":"2000","unstructured":"Inoue K, Shimotake T, Iwai N (2000) Mutational analysis of RET\/GDNF\/NTN genes in children with total colonic aganglionosis with small bowel involvement. Am J Med Genet 93:278\u2013284","journal-title":"Am J Med Genet"},{"key":"3731_CR39","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1002\/(SICI)1098-1004(200005)15:5<418::AID-HUMU3>3.0.CO;2-2","volume":"15","author":"RM Hofstra","year":"2000","unstructured":"Hofstra RM, Wu Y, Stulp RP et al (2000) RET and GDNF gene scanning in Hirschsprung patients using two dual denaturing gel systems. Hum Mutat 15:418\u2013429","journal-title":"Hum Mutat"},{"key":"3731_CR40","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/sj.ejhg.5200650","volume":"9","author":"MG Julies","year":"2001","unstructured":"Julies MG, Moore SW, Kotze MJ, du Plessis L (2001) Novel RET mutations in Hirschsprung\u2019s disease patients from the diverse South African population. Eur J Hum Genet 9:419\u2013423","journal-title":"Eur J Hum Genet"},{"key":"3731_CR41","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/S0140-6736(02)08218-1","volume":"359","author":"G Fitze","year":"2002","unstructured":"Fitze G, Cramer J, Ziegler A et al (2002) Association between c135G\/A genotype and RET proto-oncogene germline mutations and phenotype of Hirschsprung\u2019s disease. Lancet 359:1200\u20131205","journal-title":"Lancet"},{"key":"3731_CR42","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1053\/jpsu.2003.50087","volume":"38","author":"V Solari","year":"2003","unstructured":"Solari V, Ennis S, Yoneda A et al (2003) Mutation analysis of the RET gene in total intestinal aganglionosis by wave DNA fragment analysis system. J Pediatr Surg 38:497\u2013501","journal-title":"J Pediatr Surg"},{"key":"3731_CR43","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3748\/wjg.v11.i2.275","volume":"11","author":"T Guan","year":"2005","unstructured":"Guan T, Li JC, Li MJ, Tou JF (2005) Polymerase chain reaction-single strand conformational polymorphism analysis of rearranged during transfection proto-oncogene in Chinese familial Hirschsprung\u2019s disease. World J Gastroenterol 11:275\u2013279","journal-title":"World J Gastroenterol"},{"key":"3731_CR44","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1007\/s10038-006-0064-7","volume":"51","author":"S Sangkhathat","year":"2006","unstructured":"Sangkhathat S, Kusafuka T, Chengkriwate P, Patrapinyokul S, Sangthong B, Fukuzawa M (2006) Mutations and polymorphisms of Hirschsprung disease candidate genes in Thai patients. J Hum Genet 51:1126\u20131132","journal-title":"J Hum Genet"},{"key":"3731_CR45","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s10528-007-9093-y","volume":"45","author":"XN Zhang","year":"2007","unstructured":"Zhang XN, Zhou MN, Qiu YQ, Ding SP, Qi M, Li JC (2007) Genetic analysis of RET, EDNRB, and EDN3 genes and three SNPs in MCS + 9.7 in Chinese Patients with isolated Hirschsprung disease. Biochem Genet 45:523\u2013527","journal-title":"Biochem Genet"},{"key":"3731_CR46","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/S1726-4901(08)70091-1","volume":"71","author":"TW Chin","year":"2008","unstructured":"Chin TW, Chiu CY, Tsai HL, Liu CS, Wei CF, Jap TS (2008) Analysis of the RET gene in subjects with sporadic Hirschsprung\u2019s disease. J Chin Med Assoc 71:406\u2013410","journal-title":"J Chin Med Assoc"},{"key":"3731_CR47","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s00383-012-3196-1","volume":"29","author":"K Ishii","year":"2013","unstructured":"Ishii K, Doi T, Inoue K et al (2013) Correlation between multiple RET mutations and severity of Hirschsprung\u2019s disease. Pediatr Surg Int 29:157\u2013163","journal-title":"Pediatr Surg Int"},{"key":"3731_CR48","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/S0022-3468(97)90615-1","volume":"32","author":"T Shimotake","year":"1997","unstructured":"Shimotake T, Iwai N, Inoue K et al (1997) Germline mutation of the RET proto-oncogene in children with total intestinal aganglionosis. J Pediatr Surg 32:498\u2013500","journal-title":"J Pediatr Surg"}],"container-title":["Pediatric Surgery International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00383-015-3731-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00383-015-3731-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00383-015-3731-y","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T04:44:58Z","timestamp":1566967498000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00383-015-3731-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,12]]},"references-count":48,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["3731"],"URL":"https:\/\/doi.org\/10.1007\/s00383-015-3731-y","relation":{},"ISSN":["0179-0358","1437-9813"],"issn-type":[{"value":"0179-0358","type":"print"},{"value":"1437-9813","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,12]]}}}