{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T19:28:52Z","timestamp":1694114932313},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2009,11,19]],"date-time":"2009-11-19T00:00:00Z","timestamp":1258588800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genet"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Hirschsprung disease (HSCR) is a congenital malformation of the hindgut produced by a disruption in neural crest cell migration during embryonic development. HSCR has a complex genetic etiology and mutations in several genes, mainly the <jats:italic>RET<\/jats:italic> proto-oncogene, have been related to the disease. There is a clear predominance of missense\/nonsense mutations in these genes whereas copy number variations (CNVs) have been seldom described, probably due to the limitations of conventional techniques usually employed for mutational analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In this study we have aimed to analyze the presence of CNVs in some HSCR genes (RET, EDN3, GDNF and ZFHX1B) using the Multiple Ligation-dependent Probe Amplification (MLPA) approach.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Two alterations in the MLPA profiles of <jats:italic>RET<\/jats:italic> and <jats:italic>EDN3<\/jats:italic> were detected, but a detailed inspection showed that the decrease in the corresponding dosages were due to point mutations affecting the hybridization probes regions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our results indicate that CNVs of the gene coding regions analyzed here are not a common molecular cause of Hirschsprung disease. However, further studies are required to determine the presence of CNVs affecting non-coding regulatory regions, as well as other candidate genes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2350-10-119","type":"journal-article","created":{"date-parts":[[2009,11,19]],"date-time":"2009-11-19T19:46:00Z","timestamp":1258659960000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A novel study of Copy Number Variations in Hirschsprung disease using the Multiple Ligation-dependent Probe Amplification (MLPA) technique"],"prefix":"10.1186","volume":"10","author":[{"given":"Roc\u00edo","family":"N\u00fa\u00f1ez-Torres","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel M","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"L\u00f3pez-Alonso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Anti\u00f1olo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salud","family":"Borrego","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2009,11,19]]},"reference":[{"key":"533_CR1","first-page":"6231","volume-title":"The metabolic and molecular bases of inherited disease","author":"A Chakravarti","year":"2002","unstructured":"Chakravarti A, Lyonnet S: Hirschsprung Disease. The metabolic and molecular bases of inherited disease. Edited by: Scriver CS. 2002, McGraw-Hill, 6231-6255."},{"key":"533_CR2","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, Pelet A, Arnold S, Miao X, Griseri P, Brooks AS, Antinolo G, de Pontual L, Clement-Ziza M, Munnich A, Kashuk C, West K, Wong KK, Lyonnet S, Chakravarti A, Tam PK, Ceccherini I, Hofstra RM, Fernandez R, Hirschsprung Disease Consortium: Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet. 2008, 45: 1-14. 10.1136\/jmg.2007.053959.","journal-title":"J Med Genet"},{"key":"533_CR3","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1038\/nature03467","volume":"434","author":"ES Emison","year":"2005","unstructured":"Emison ES, McCallion AS, Kashuk CS, Bush RT, Grice E, Lin S, Portnoy ME, Cutler DJ, Green ED, Chakravarti A: A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. Nature. 2005, 434: 857-63. 10.1038\/nature03467.","journal-title":"Nature"},{"key":"533_CR4","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1016\/j.jpedsurg.2008.02.076","volume":"43","author":"M Ruiz-Ferrer","year":"2008","unstructured":"Ruiz-Ferrer M, Fernandez RM, Anti\u00f1olo G, Lopez-Alonso M, Borrego S: NTF-3, a gene involved in the enteric nervous system development, as a candidate gene for Hirschsprung disease. J Pediatr Surg. 2008, 43: 1308-11. 10.1016\/j.jpedsurg.2008.02.076.","journal-title":"J Pediatr Surg"},{"key":"533_CR5","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/j.1469-1809.2008.00479.x","volume":"73","author":"RM Fern\u00e1ndez","year":"2009","unstructured":"Fern\u00e1ndez RM, S\u00e1nchez-Mej\u00edas A, Mena MD, Ruiz-Ferrer M, L\u00f3pez-Alonso M, Anti\u00f1olo G, Borrego S: A novel point variant in NTRK3, R645C, suggests a role of this gene in the pathogenesis of Hirschsprung disease. Ann Hum Genet. 2009, 73: 19-25. 10.1111\/j.1469-1809.2008.00479.x.","journal-title":"Ann Hum Genet"},{"key":"533_CR6","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1159\/000472232","volume":"4","author":"L Yin","year":"1996","unstructured":"Yin L, Seri M, Barone V, Tocco T, Scaranari M, Romeo G: Prevalence and parental origin of de novo RET mutations in Hirschsprung's disease. Eur J Hum Genet. 1996, 4: 356-8.","journal-title":"Eur J Hum Genet"},{"key":"533_CR7","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1002\/humu.20035","volume":"23","author":"LN Sellner","year":"2004","unstructured":"Sellner LN, Taylor GR: MLPA and MAPH: new techniques for detection of gene deletions. Hum Mutat. 2004, 23: 413-9. 10.1002\/humu.20035.","journal-title":"Hum Mutat"},{"key":"533_CR8","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1097\/01.gim.0000245632.06064.f1","volume":"8","author":"M Ruiz-Ferrer","year":"2006","unstructured":"Ruiz-Ferrer M, Fern\u00e1ndez RM, Anti\u00f1olo G, L\u00f3pez-Alonso M, Eng C, Borrego S: A complex additive model of inheritance for Hirschsprung disease is supported by both RET mutations and predisposing RET haplotypes. Genet Med. 2006, 8: 704-10.","journal-title":"Genet Med"},{"key":"533_CR9","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1136\/jmg.2004.023960","volume":"42","author":"RM Fernandez","year":"2005","unstructured":"Fernandez RM, Boru G, Pecina A, Jones K, Lopez-Alonso M, Antinolo G, Borrego S, Eng C: Ancestral RET haplotype associated with Hirschsprung's disease shows linkage disequilibrium breakpoint at -1249. J Med Genet. 2005, 42: 322-7. 10.1136\/jmg.2004.023960.","journal-title":"J Med Genet"},{"key":"533_CR10","volume-title":"J Med Genet","author":"A Sanchez-Mejias","year":"2009","unstructured":"Sanchez-Mejias A, Fernandez RM, Lopez-Alonso M, Antinolo G, Borrego S: Contribution of RET, NTRK3 and EDN3 to the expression of Hirschsprung disease in a multiplex family. 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Gen Med."}],"container-title":["BMC Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2350-10-119.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2350-10-119\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2350-10-119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2350-10-119.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:52:42Z","timestamp":1630457562000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedgenet.biomedcentral.com\/articles\/10.1186\/1471-2350-10-119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11,19]]},"references-count":11,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["533"],"URL":"https:\/\/doi.org\/10.1186\/1471-2350-10-119","relation":{},"ISSN":["1471-2350"],"issn-type":[{"value":"1471-2350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,19]]},"assertion":[{"value":"2 February 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2009","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2009","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"119"}}