{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:00:56Z","timestamp":1774418456408,"version":"3.50.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2008,6,6]],"date-time":"2008-06-06T00:00:00Z","timestamp":1212710400000},"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":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Genetic factors make an important contribution to the aetiology of congenital talipes equinovarus (CTEV), the most common developmental disorder of the lower limb. WNT7A was suggested as a candidate gene for CTEV on the basis of a genome-wide scan for linkage in a large multi-case family. WNT7A is a plausible candidate gene for CTEV as it provides a signal for pattern formation during limb development, and mutation in WNT7A has been reported in a number of limb malformation syndromes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We investigated the role of WNT7A using a family-based linkage approach in our large series of European multi-case CTEV families. Three microsatellite markers were used, of which one (D3S2385) is intragenic, and the other two (D3S2403, D3S1252) are 700 kb 5' to the start and 20 kb from the 3' end of the gene, respectively. Ninety-one CTEV families, comprising 476 individuals of whom 211 were affected, were genotyped. LOD scores using recessive and incomplete-dominant inheritance models, and non-parametric linkage scores, excluded linkage.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>No significant evidence for linkage was observed using either parametric or non-parametric models. LOD scores for the parametric models remained strongly negative in the regions between the markers, and in the 0.5 cM intervals outside the marker map. No significant lod scores were obtained when the data were analysed allowing for heterogeneity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our evidence suggests that the WNT7A gene is unlikely to be a major contributor to the aetiology of familial CTEV.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2350-9-50","type":"journal-article","created":{"date-parts":[[2008,6,6]],"date-time":"2008-06-06T18:13:37Z","timestamp":1212776017000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Variation in WNT7A is unlikely to be a cause of familial Congenital Talipes Equinovarus"],"prefix":"10.1186","volume":"9","author":[{"given":"Guoqing","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Inglis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Cardy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duncan","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukhy","family":"Sahota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raoul","family":"Hennekam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Sharp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zosia","family":"Miedzybrodzka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2008,6,6]]},"reference":[{"key":"344_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1046\/j.1469-7580.2003.00147.x","volume":"202","author":"Z Miedzybrodzka","year":"2003","unstructured":"Miedzybrodzka Z: Congenital talipes equinovarus (clubfoot): A disorder of the foot but not the hand. J Anat. 2003, 202: 37-42. 10.1046\/j.1469-7580.2003.00147.x.","journal-title":"J Anat"},{"key":"344_CR2","first-page":"66","volume":"40","author":"RW Porter","year":"1995","unstructured":"Porter RW: Clubfoot: congenital talipes equinovarus. Journal of the Royal College of Surgeons of Edinburgh. 1995, 40: 66-71.","journal-title":"Journal of the Royal College of Surgeons of Edinburgh"},{"key":"344_CR3","first-page":"772","volume":"42","author":"J Wang","year":"1988","unstructured":"Wang J, Palmer RM, Chung CS: The role of major gene in clubfoot. Am J Hum Genet. 1988, 42: 772-776.","journal-title":"Am J Hum Genet"},{"key":"344_CR4","first-page":"1051","volume":"53","author":"TR Rebbeck","year":"1993","unstructured":"Rebbeck TR, Dietz FR, Murray JC, Buetow KH: A single-gene explanation for the probability of having idiopathic talipes equinovarus. Am J Hum Genet. 1993, 53: 1051-1063.","journal-title":"Am J Hum Genet"},{"key":"344_CR5","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1002\/(SICI)1096-8628(19980901)79:2<97::AID-AJMG4>3.0.CO;2-K","volume":"79","author":"M de Andrade","year":"1998","unstructured":"de Andrade M, Barnholtz JS, Amos CI, Lochmiller C, Scott A, Risman M, Hecht JT: Segregation analysis of idiopathic talipes equinovarus in Texan population. Am J Med Genet. 1998, 79: 97-102. 10.1002\/(SICI)1096-8628(19980901)79:2<97::AID-AJMG4>3.0.CO;2-K.","journal-title":"Am J Med Genet"},{"key":"344_CR6","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/0092-8674(92)90222-X","volume":"69","author":"AP McMahon","year":"1992","unstructured":"McMahon AP, Joyner AL, Bradley A, McMahon JA: The midbrain-hindbrain phenotype of Wnt-1-\/Wnt-1- mice results from stepwise deletion of engrailed-expressing cells by 9.5 days postcoitum. Cell. 1992, 69: 581-595. 10.1016\/0092-8674(92)90222-X.","journal-title":"Cell"},{"key":"344_CR7","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1126\/science.287.5458.1606","volume":"287","author":"M Peifer","year":"2000","unstructured":"Peifer M, Polakis P: Wnt signaling in oncogenesis and embryogenesis-a look outside the nucleus. Science. 2000, 287: 1606-1609. 10.1126\/science.287.5458.1606.","journal-title":"Science"},{"key":"344_CR8","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/0092-8674(92)90630-U","volume":"69","author":"R Nusse","year":"1992","unstructured":"Nusse R, Varmus HE: Wnt genes. Cell. 1992, 69: 1073-1087. 10.1016\/0092-8674(92)90630-U.","journal-title":"Cell"},{"key":"344_CR9","first-page":"927","volume":"46","author":"VL Church","year":"2002","unstructured":"Church VL, Francis-West P: Wnt signalling during limb development. Int J Dev Biol. 2002, 46: 927-936.","journal-title":"Int J Dev Biol"},{"key":"344_CR10","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/374350a0","volume":"374","author":"BA Parr","year":"1995","unstructured":"Parr BA, McMahon AP: Dorsalizing signal Wnt-7a required for normal polarity of D-V and A-P axes of mouse limb. Nature. 1995, 374: 350-353. 10.1038\/374350a0.","journal-title":"Nature"},{"key":"344_CR11","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/0092-8674(95)90103-5","volume":"83","author":"RD Riddle","year":"1995","unstructured":"Riddle RD, Ensini M, Nelson C, Tsuchida T, Jessell TM, Tabin C: Induction of the LIM homeobox gene Lmx I by WNT7a establishes dorsoventral pattern in the vertebrate limb. Cell. 1995, 83: 631-640. 10.1016\/0092-8674(95)90103-5.","journal-title":"Cell"},{"key":"344_CR12","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1096\/fj.00-0784fje","volume":"15","author":"AC Tufan","year":"2001","unstructured":"Tufan AC, Tuan RS: Wnt regulation of limb mesenchymal chondrogenesis is accompanied by altered N-cadherin-related functions. FASEB J. 2001, 15: 1436-1438.","journal-title":"FASEB J"},{"key":"344_CR13","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1086\/506332","volume":"79","author":"CG Woods","year":"2006","unstructured":"Woods CG, Stricker S, Seemann P, Stern R, Cox J, Sherridan E, Roberts E, Springell K, Scott S, Karbani G, Sharif SM, Toomes C, Bond J, Kumar D, Al-Gazali L, Mundlos S: Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi\/Raas-Rothschild\/Schinzel phocomelia syndrome. Am J Hum Genet. 2006, 79: 402-408. 10.1086\/506332.","journal-title":"Am J Hum Genet"},{"key":"344_CR14","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/0092-8674(95)90297-X","volume":"80","author":"Y Yang","year":"1995","unstructured":"Yang Y, Niswander L: Interaction between the signaling molecules WNT7a and SHH during vertebrate limb development: Dorsal signals regulate anteroposterior patterning. Cell. 1995, 80: 939-947. 10.1016\/0092-8674(95)90297-X.","journal-title":"Cell"},{"key":"344_CR15","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1111\/j.1399-0004.2005.00407.x","volume":"67","author":"FR Dietz","year":"2005","unstructured":"Dietz FR, Cole WG, Tosi LL, Carroll NC, Wemer RD, Comstock D, Murray JC: A search for the gene(s) predisposing to idiopathic clubfoot. Clin Genet. 2005, 67: 361-362. 10.1111\/j.1399-0004.2005.00407.x.","journal-title":"Clin Genet"},{"key":"344_CR16","first-page":"1347","volume":"58","author":"L Kruglyak","year":"1996","unstructured":"Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES: Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet. 1996, 58: 1347-63.","journal-title":"Am J Hum Genet"},{"key":"344_CR17","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1136\/jmg.37.9.680","volume":"37","author":"C Chapman","year":"2000","unstructured":"Chapman C, Stott NS, Port RV, Nicol RO: Genetics of club foot in Maori and Pacific people. J Med Genet. 2000, 37: 680-683. 10.1136\/jmg.37.9.680.","journal-title":"J Med Genet"},{"key":"344_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/(SICI)1520-6408(1996)19:1<1::AID-DVG1>3.0.CO;2-D","volume":"19","author":"C Tickle","year":"1996","unstructured":"Tickle C: Genetics and limb development. Dev Genet. 1996, 19: 1-8. 10.1002\/(SICI)1520-6408(1996)19:1<1::AID-DVG1>3.0.CO;2-D.","journal-title":"Dev Genet"},{"key":"344_CR19","first-page":"621","volume":"36","author":"A Superti-Furga","year":"1999","unstructured":"Superti-Furga A, Neumann L, Riebel T, Eich G, Steinmann B, Spranger J, Kunze J: Recessively inherited multiple epiphyseal dysplasia with normal stature, club foot, and double layered patella caused by a DTDST mutation. J Med Genet. 1999, 36: 621-624.","journal-title":"J Med Genet"},{"key":"344_CR20","doi-asserted-by":"publisher","first-page":"e20","DOI":"10.1136\/jmg.39.4.e20","volume":"39","author":"L Bonafe","year":"2002","unstructured":"Bonafe L, Blanton SH, Scott A, Broussard S, Wise CA, Superti-Furga A, Hecht JT: DTDST mutations are not a frequent cause of idiopathic talipes equinovarus (club foot). J Med Genet. 2002, 39: e20-10.1136\/jmg.39.4.e20.","journal-title":"J Med Genet"},{"key":"344_CR21","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1002\/jor.20052","volume":"24","author":"MB Dobbs","year":"2006","unstructured":"Dobbs MB, Gurnett CA, Pierce B, Exner GU, Robarge J, Morcuende JA, Cole WG, Templeton PA, Foster B, Bowcock AM: HOXD10 M319K mutation in a family with isolated congenital vertical talus. J Orthop Res. 2006, 24: 448-453. 10.1002\/jor.20052.","journal-title":"J Orthop Res"},{"key":"344_CR22","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1097\/BLO.0b013e31805d8649","volume":"462","author":"CA Gurnett","year":"2007","unstructured":"Gurnett CA, Keppel C, Bick J, Bowcock AM, Dobbs MB: Absence of HOXD10 mutations in idiopathic clubfoot and sporadic vertical talus. Clin Orthop Relat Res. 2007, 462: 27-31. 10.1097\/BLO.0b013e31805d8649.","journal-title":"Clin Orthop Relat Res"},{"key":"344_CR23","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1097\/01.bpo.0000173248.96936.90","volume":"25","author":"AL Heck","year":"2005","unstructured":"Heck AL, Bray MS, Scott A, Blanton SH, Hecht JT: Variation in CASP10 gene is associated with idiopathic talipes equinovarus. J Pediatr Orthop. 2005, 25: 598-602. 10.1097\/01.bpo.0000173248.96936.90.","journal-title":"J Pediatr Orthop"},{"key":"344_CR24","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1097\/BLO.0b013e318073c2d9","volume":"462","author":"AR Ester","year":"2007","unstructured":"Ester AR, Tyerman G, Wise CA, Blanton SH, Hecht JT: Apoptotic gene analysis in idiopathic talipes equinovarus (Clubfoot). Clin Orthop Relat Res. 2007, 462: 32-37. 10.1097\/BLO.0b013e318073c2d9.","journal-title":"Clin Orthop Relat Res"},{"key":"344_CR25","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1093\/aje\/kwj285","volume":"164","author":"L Sharp","year":"2006","unstructured":"Sharp L, Miedzybrodzka Z, Cardy AH, Inglis J, Madrigal L, Barker S, Chesney D, Clark C, Maffulli N: The C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR), maternal use of folic acid supplements, and risk of isolated clubfoot: A case-parent-triad analysis. Am J Epidemiology. 2006, 164: 852-861. 10.1093\/aje\/kwj285.","journal-title":"Am J Epidemiology"},{"key":"344_CR26","doi-asserted-by":"publisher","first-page":"2285","DOI":"10.1002\/ajmg.a.31927","volume":"143","author":"JT Hecht","year":"2007","unstructured":"Hecht JT, Ester A, Scott A, Wise CA, Iovannisci DM, Lammer EJ, Langlois PH, Blanton SH: NAT2 variation and idiopathic talipes equinovarus (clubfoot). Am J Med Genet. 2007, 143: 2285-2291. 10.1002\/ajmg.a.31927.","journal-title":"Am J Med Genet"},{"key":"344_CR27","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1086\/302011","volume":"63","author":"KW Broman","year":"1998","unstructured":"Broman KW, Murray JC, Sheffield VC, White RL, Weber JL: Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am J Hum Genet. 1998, 63: 861-869. 10.1086\/302011.","journal-title":"Am J Hum Genet"}],"container-title":["BMC Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2350-9-50.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2350-9-50\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2350-9-50","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2350-9-50.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T02:47:24Z","timestamp":1630464444000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedgenet.biomedcentral.com\/articles\/10.1186\/1471-2350-9-50"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6,6]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["344"],"URL":"https:\/\/doi.org\/10.1186\/1471-2350-9-50","relation":{},"ISSN":["1471-2350"],"issn-type":[{"value":"1471-2350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6,6]]},"assertion":[{"value":"28 September 2007","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2008","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2008","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"50"}}