{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:58:52Z","timestamp":1760403532857,"version":"build-2065373602"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81702081"],"award-info":[{"award-number":["81702081"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["18ZR1424600 17ZR1417900"],"award-info":[{"award-number":["18ZR1424600 17ZR1417900"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Polydactyly and syndactyly are the most common hereditary limb malformations. Molecular genetic testing is of great significance for hereditary limb malformations, which can establish prognosis and recurrence risk of surgical intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The present study aimed to identify the genetic etiologies of a three\u2010generation family with postaxial polydactyly and a four\u2010generation family with postaxial syndactyly. Whole exome sequencing was used, followed by standard mutation screening procedure, Sanger sequencing and bioinformatics analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two nonframeshifting insertion\/deletion (indel) mutations in <jats:italic>HOXD13<\/jats:italic> (c.206_207ins AGCGGCGGCTGCGGCGGCGGCGGC:p.A68insAAAAAAAA or c.171_182delGGCGGCGGCGGC: p.56_60delAAAA) were successfully identified as the pathogenic mutation. The two nonframeshifting indel mutations led to truncation or expansion of homopolymeric alanine (Poly\u2010Ala) repeats of HOXD13 proteins. Sequence alignment of HOXD13 protein among many different species for Poly\u2010Ala position is highly conserved. Hypothetical three\u2010dimensional (3\u2010D) structural analysis further showed mutant HOXD13 proteins (p.A68insAAAAAAAA and p.56_60delAAAA) converted the disordered fragment into a short \u03b2\u2010strand (residues 63\u201068 or residues 64\u201068), thereby forming a conformational change.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study identified two nonframeshifting mutations of <jats:italic>HOXD13<\/jats:italic> polyalanine repeat location in two Chinese families with postaxial polydactyly or postaxial syndactyly. Our results also provide new insights into genetic counseling and clinical management.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.310","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T19:36:55Z","timestamp":1612553815000},"page":"1220-1228","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nonframeshifting indel variations in polyalanine repeat of <scp><i>HOXD13<\/i><\/scp> gene underlies hereditary limb malformation for two Chinese families"],"prefix":"10.1002","volume":"250","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2201-2657","authenticated-orcid":false,"given":"Bailing","family":"Zu","sequence":"first","affiliation":[{"name":"Pediatric Translational Medicine Institute, Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Orthopedic Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunlan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Orthopedic Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoling","family":"You","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qihua","family":"Fu","sequence":"additional","affiliation":[{"name":"Pediatric Translational Medicine Institute, Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0000000000001499"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000472392"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2019.09.023"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.14"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2018.18"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.08.005"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/hgv.2017.54"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-014-0110-9"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.018"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-018-0570-z"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.081174"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16317-2"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00396"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6576"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.249.93"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.07.039"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/511387"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.157610.113"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/374721"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096192"},{"issue":"7","key":"e_1_2_8_22_1","first-page":"13200","article-title":"Phenotype and HOXD13 gene mutation in a big synpolydactyly (SPD) pedigree","volume":"9","author":"Chen X","year":"2016","journal-title":"Int J Clin Exp Med"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2012.02.046"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.066027"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.7.945"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30971"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31967"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.4.e49"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-8-78"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2007.00935.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2011.84"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.10.042"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.86"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg0720s76"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0810-575"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msy096"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3213"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3235"}],"container-title":["Developmental Dynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvdy.310","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/dvdy.310","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvdy.310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T17:34:22Z","timestamp":1760376862000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/dvdy.310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,30]]},"references-count":41,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1002\/dvdy.310"],"URL":"https:\/\/doi.org\/10.1002\/dvdy.310","archive":["Portico"],"relation":{},"ISSN":["1058-8388","1097-0177"],"issn-type":[{"type":"print","value":"1058-8388"},{"type":"electronic","value":"1097-0177"}],"subject":[],"published":{"date-parts":[[2021,3,30]]},"assertion":[{"value":"2020-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}