{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T22:24:37Z","timestamp":1772835877828,"version":"3.50.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T00:00:00Z","timestamp":1504137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T00:00:00Z","timestamp":1504137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hum Genet"],"published-print":{"date-parts":[[2017,12]]},"DOI":"10.1038\/jhg.2017.86","type":"journal-article","created":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T06:20:53Z","timestamp":1504160453000},"page":"1073-1078","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Santos syndrome is caused by mutation in the WNT7A gene"],"prefix":"10.1038","volume":"62","author":[{"given":"Leandro U","family":"Alves","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvana","family":"Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila M","family":"Musso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzana AM","family":"Ezquina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M","family":"Opitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Kok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo A","family":"Otto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina C","family":"Mingroni-Netto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,8,31]]},"reference":[{"key":"BFjhg201786_CR1","doi-asserted-by":"publisher","first-page":"3126","DOI":"10.1002\/ajmg.a.32580","volume":"146A","author":"SC Santos","year":"2008","unstructured":"Santos, S. C., Pardono, E., Ferreira da Costa, M. I., de Melo, A. N., Graciani, Z., de Albuquerque e Souza, A. C. et al. A previously undescribed syndrome combining fibular agenesis\/hypoplasia, oligodactylous clubfeet, anonychia\/ungual hypoplasia, and other defects. Am. J. Med. Genet. A 146A, 3126\u20133131 (2008).","journal-title":"Am. J. Med. Genet. A"},{"key":"BFjhg201786_CR2","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1002\/ajmg.1320250626","volume":"2","author":"SO Lewin","year":"1986","unstructured":"Lewin, S. O. & Opitz, J. M. Fibular a\/hypoplasia: review and documentation of the fibular developmental field. Am. J. Med. Genet. Suppl. 2, 215\u2013238 (1986).","journal-title":"Am. J. Med. Genet. Suppl."},{"key":"BFjhg201786_CR3","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1111\/j.1399-0004.1990.tb03589.x","volume":"38","author":"M Genuardi","year":"1990","unstructured":"Genuardi, M., Zollino, M., Bellussi, A., Fuhrmann, W. & Neri, G. Brachy\/ectrodactyly and absence or hypoplasia of the fibula: an autosomal dominant condition with low penetrance and variable expressivity. Clin. Genet. 38, 321\u2013326 (1990).","journal-title":"Clin. Genet."},{"key":"BFjhg201786_CR4","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1002\/ajmg.10754","volume":"113","author":"JA Evans","year":"2002","unstructured":"Evans, J. A., Reed, M. H. & Greenberg, C. R. Fibular aplasia with ectrodactyly. Am. J. Med. Genet. 113, 52\u201358 (2002).","journal-title":"Am. J. Med. Genet."},{"key":"BFjhg201786_CR5","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/BF00441580","volume":"133","author":"W Fuhrmann","year":"1980","unstructured":"Fuhrmann, W., Fuhrmann-Rieger, A. & de Sousa, F. Poly-, syn- and oligodactyly, aplasia or hypoplasia of fibula, hypoplasia of pelvis and bowing of femora in three sibs\u2014a new autosomal recessive syndrome. Eur. J. Pediatr. 133, 123\u2013129 (1980).","journal-title":"Eur. J. Pediatr."},{"key":"BFjhg201786_CR6","first-page":"519","volume":"104","author":"W Fuhrmann","year":"1982","unstructured":"Fuhrmann, W., Fuhrmann-Rieger, A., Jovanovi\u0107, V. & Rehder, H. A new autosomal recessive skeletal dysplasia syndrome\u2014prenatal diagnosis and histopathology. Prog. Clin. Biol. Res. 104, 519\u2013524 (1982).","journal-title":"Prog. Clin. Biol. Res."},{"key":"BFjhg201786_CR7","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1002\/ajmg.1320290422","volume":"29","author":"RA Pfeiffer","year":"1988","unstructured":"Pfeiffer, R. A., St\u00f6ss, H., Voight, H. J. & W\u00fcndisch, G. F. Absence of fibula and ulna with oligodactyly, contractures, right-angle bowing of femora, abnormal facial morphology, cleft lip\/palate and brain malformation in two sibs: a possibly new lethal syndrome. Am. J. Med. Genet. 29, 901\u2013908 (1988).","journal-title":"Am. J. Med. Genet."},{"key":"BFjhg201786_CR8","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1086\/506332","volume":"79","author":"CG Woods","year":"2006","unstructured":"Woods, C. G., Stricker, S., Seemann, P., Stern, R., Cox, J., Sherridan, E. et al. Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi\/Raas-Rothschild\/Schinzel phocomelia syndrome. Am. J. Hum. Genet. 79, 402\u2013408 (2006).","journal-title":"Am. J. Hum. Genet."},{"key":"BFjhg201786_CR9","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1590\/S1415-47572010005000020","volume":"33","author":"S Santos","year":"2010","unstructured":"Santos, S., Kok, F., Weller, M., de Paiva, F. R. & Otto, P. A. Inbreeding levels in Northeast Brazil: strategies for the prospecting of new genetic disorders. Genet. Mol. Biol. 33, 220\u2013223 (2010).","journal-title":"Genet. Mol. Biol."},{"key":"BFjhg201786_CR10","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1002\/ajhb.22328","volume":"24","author":"M Weller","year":"2012","unstructured":"Weller, M., Tanieri, M., Pereira, J. C., Almeida Edos, S., Kok, F. & Santos, S. Consanguineous unions and the burden of disability: a population-based study in communities of Northeastern Brazil. Am. J. Hum. Biol. 24, 835\u2013840 (2012).","journal-title":"Am. J. Hum. Biol."},{"key":"BFjhg201786_CR11","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/ng786","volume":"30","author":"GR Abecasis","year":"2002","unstructured":"Abecasis, G. R., Cherny, S. S., Cookson, W. O. & Cardon, L. R. Merlin\u2014rapid analysis of dense genetic maps using sparse gene flow trees. Nat. Genet. 30, 97\u2013101 (2002).","journal-title":"Nat. Genet."},{"key":"BFjhg201786_CR12","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009).","journal-title":"Bioinformatics"},{"key":"BFjhg201786_CR13","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297\u20131303 (2010).","journal-title":"Genome Res."},{"key":"BFjhg201786_CR14","doi-asserted-by":"publisher","first-page":"e164","DOI":"10.1093\/nar\/gkq603","volume":"38","author":"K Wang","year":"2010","unstructured":"Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).","journal-title":"Nucleic Acids Res."},{"key":"BFjhg201786_CR15","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","volume":"7","author":"IA Adzhubei","year":"2010","unstructured":"Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P. et al. A method and server for predicting damaging missense mutations. Nat. Methods 7, 248\u2013249 (2010).","journal-title":"Nat. Methods"},{"key":"BFjhg201786_CR16","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1146\/annurev.genom.7.080505.115630","volume":"7","author":"PC Ng","year":"2006","unstructured":"Ng, P. C. & Henikoff, S. Predicting the effects of amino acid substitutions on protein function. Annu. Rev. Genomics Hum. Genet. 7, 61\u201380 (2006).","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"BFjhg201786_CR17","doi-asserted-by":"publisher","first-page":"e46688","DOI":"10.1371\/journal.pone.0046688","volume":"7","author":"Y Choi","year":"2012","unstructured":"Choi, Y., Sims, G. E., Murphy, S., Miller, J. R. & Chan, A. P. Predicting the functional effect of amino acid substitutions and indels. PLoS ONE 7, e46688 (2012).","journal-title":"PLoS ONE"},{"key":"BFjhg201786_CR18","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/nmeth.2890","volume":"11","author":"JM Schwarz","year":"2014","unstructured":"Schwarz, J. M., Cooper, D. N., Schuelke, M. & Seelow, D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat. Methods 11, 361\u2013362 (2014).","journal-title":"Nat. Methods"},{"key":"BFjhg201786_CR19","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nrg1001","volume":"4","author":"L Niswander","year":"2003","unstructured":"Niswander, L. Pattern formation: old models out on a limb. Nat. Rev. Genet. 4, 133\u2013143 (2003).","journal-title":"Nat. Rev. Genet."},{"key":"BFjhg201786_CR20","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/371609a0","volume":"371","author":"L Niswander","year":"1994","unstructured":"Niswander, L., Jeffrey, S., Martin, G. R. & Tickle, C. A positive feedback loop coordinates growth and patterning in the vertebrate limb. Nature 371, 609\u2013612 (1994).","journal-title":"Nature"},{"key":"BFjhg201786_CR21","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/nature00902","volume":"418","author":"X Sun","year":"2002","unstructured":"Sun, X., Mariani, F. V. & Martin, G. R. Functions of FGF signalling from the apical ectodermal ridge in limb development. Nature 418, 501\u2013508 (2002).","journal-title":"Nature"},{"key":"BFjhg201786_CR22","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/289295a0","volume":"289","author":"C Tickle","year":"1981","unstructured":"Tickle, C. The number of polarizing region cells required to specify additional digits in the developing chick wing. Nature 289, 295\u2013298 (1981).","journal-title":"Nature"},{"key":"BFjhg201786_CR23","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1016\/0092-8674(93)90626-2","volume":"75","author":"RD Riddle","year":"1993","unstructured":"Riddle, R. D., Johnson, R. L., Laufer, E. & Tabin, C. Sonic hedgehog mediates the polarizing activity of the ZPA. Cell 75, 1401\u20131416 (1993).","journal-title":"Cell"},{"key":"BFjhg201786_CR24","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/44157","volume":"401","author":"A Z\u00fa\u00f1iga","year":"1999","unstructured":"Z\u00fa\u00f1iga, A., Haramis, A. P., McMahon, A. P. & Zeller, R. Signal relay by BMP antagonism controls the SHH\/FGF4 feedback loop in vertebrate limb buds. Nature 401, 598\u2013602 (1999).","journal-title":"Nature"},{"key":"BFjhg201786_CR25","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/0092-8674(95)90103-5","volume":"83","author":"RD Riddle","year":"1995","unstructured":"Riddle, R. D., Ensini, M., Nelson, C., Tsuchida, T., Jessell, T. M. & Tabin, C. Induction of the LIM homeobox gene Lmx1 by WNT7a establishes dorsoventral pattern in the vertebrate limb. Cell 83, 631\u2013640 (1995).","journal-title":"Cell"},{"key":"BFjhg201786_CR26","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/374350a0","volume":"374","author":"BA Parr","year":"1995","unstructured":"Parr, B. A. & McMahon, A. P. Dorsalizing signal Wnt-7a required for normal polarity of D-V and A-P axes of mouse limb. Nature 374, 350\u2013353 (1995).","journal-title":"Nature"},{"key":"BFjhg201786_CR27","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1002\/ajmg.a.33793","volume":"155A","author":"L Garavelli","year":"2011","unstructured":"Garavelli, L., Wischmeijer, A., Rosato, S., Gelmini, C., Reverberi, S., Sassi, S. et al. Al-Awadi-Raas-Rothschild (limb\/pelvis\/uterus-hypoplasia\/aplasia) syndrome and WNT7A mutations: genetic homogeneity and nosological delineation. Am. J. Med. Genet. A 155A, 332\u2013336 (2011).","journal-title":"Am. J. Med. Genet. A"},{"key":"BFjhg201786_CR28","doi-asserted-by":"publisher","first-page":"2832","DOI":"10.1002\/ajmg.a.33673","volume":"152A","author":"PN Kantaputra","year":"2010","unstructured":"Kantaputra, P. N., Mundlos, S. & Sripathomsawat, W. A novel homozygous Arg222Trp missense mutation in WNT7A in two sisters with severe Al-Awadi\/Raas-Rothschild\/Schinzel phocomelia syndrome. Am. J. Med. Genet. A 152A, 2832\u20132837 (2010).","journal-title":"Am. J. Med. Genet. A"},{"key":"BFjhg201786_CR29","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.gene.2013.05.023","volume":"527","author":"MM Al-Qattan","year":"2013","unstructured":"Al-Qattan, M. M., Al-Abdulkareem, I., Ballow, M. & Al Balwi, M. A report of two cases of Al-Awadi Raas-Rothschild syndrome (AARRS) supporting that \u2018apparent\u2019 phocomelia differentiates AARRS from Schinzel phocomelia syndrome (SPS). Gene 527, 371\u2013375 (2013).","journal-title":"Gene"},{"key":"BFjhg201786_CR30","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1002\/ajmg.a.33717","volume":"155A","author":"W Eyaid","year":"2011","unstructured":"Eyaid, W., Al-Qattan, M. M., Al Abdulkareem, I., Fetaini, N. & Al Balwi, M. A novel homozygous missense mutation (c.610G&gt;A, p.Gly204Ser) in the WNT7A gene causes tetra-amelia in two Saudi families. Am. J. Med. Genet. A 155A, 599\u2013604 (2011).","journal-title":"Am. J. Med. Genet. A"},{"key":"BFjhg201786_CR31","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.gene.2012.12.020","volume":"516","author":"MM Al-Qattan","year":"2013","unstructured":"Al-Qattan, M. M., Shamseldin, H. E. & Alkuraya, F. S. The WNT7A G204S mutation is associated with both Al-Awadi-Raas Rothschild syndrome and Fuhrmann syndrome phenotypes. Gene 516, 168\u2013170 (2013).","journal-title":"Gene"},{"key":"BFjhg201786_CR32","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1093\/hmg\/ddq462","volume":"20","author":"B Wang","year":"2011","unstructured":"Wang, B., Sinha, T., Jiao, K., Serra, R. & Wang, J. Disruption of PCP signaling causes limb morphogenesis and skeletal defects and may underlie Robinow syndrome and brachydactyly type B. Hum. Mol. Genet. 20, 271\u2013285 (2011).","journal-title":"Hum. Mol. Genet."},{"key":"BFjhg201786_CR33","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.1002\/ajmg.a.35437","volume":"161A","author":"MM Al-Qattan","year":"2013","unstructured":"Al-Qattan, M. M. Molecular basis of the clinical features of Al-Awadi-Raas-Rothschild (limb\/pelvis\/uterus-hypoplasia\/aplasia) syndrome (AARRS) and Fuhrmann syndrome. Am. J. Med. Genet. A 161A, 2274\u20132280 (2013).","journal-title":"Am. J. Med. Genet. A"},{"key":"BFjhg201786_CR34","first-page":"1","volume":"14","author":"SA Temtamy","year":"1978","unstructured":"Temtamy, S. A. & McKusick, V. A. The genetics of hand malformations. Birth Defects Orig. Artic. Ser. 14: i-xviii, 1\u2013619 (1978).","journal-title":"Birth Defects Orig. Artic. Ser."}],"container-title":["Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/jhg201786.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/jhg201786","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/jhg.2017.86","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/jhg201786.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T03:08:44Z","timestamp":1641006524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/jhg201786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,31]]},"references-count":34,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["BFjhg201786"],"URL":"https:\/\/doi.org\/10.1038\/jhg.2017.86","relation":{},"ISSN":["1434-5161","1435-232X"],"issn-type":[{"value":"1434-5161","type":"print"},{"value":"1435-232X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,31]]},"assertion":[{"value":"12 April 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2017","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2017","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2017","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}