{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:40:40Z","timestamp":1777660840047,"version":"3.51.4"},"reference-count":30,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Genetic Testing and Molecular Biomarkers"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Polydactyly is characterized by multiple distinct heterogeneous phenotypes, the etiologies of which involve several genes. This study aimed to explore the genetic defects and further clarify the molecular mechanism of polydactyly in several Chinese families.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Three families with diverse phenotypes of non-syndromic polydactyly were analyzed: two were cases of familial disease, whereas one was sporadic. PCR and Sanger sequencing were used to screen for pathogenic mutations in two known disease-associated genes,\n                      <jats:italic toggle=\"yes\">GLI3<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">HOXD13<\/jats:italic>\n                      , while bioinformatic analyses predicted the pathogenicity of the identified variants. Reverse transcription PCR was used to analyze the splicing effect of an intronic variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Two novel heterozygous frameshift mutations (c.4478delG\/p.S1493Tfs*18; c.846_c.847insC\/p.R283Qfs*21) were identified in the\n                      <jats:italic toggle=\"yes\">GLI3<\/jats:italic>\n                      gene from two of the pedigrees. Both c.4478delG and c.846_c.847insC were later confirmed in affected and unaffected members and normal controls, to truncate and disrupt the integrity of the\n                      <jats:italic toggle=\"yes\">GLI3<\/jats:italic>\n                      protein, reduce its level of expression, and disrupt its biological function through nonsense-mediated mRNA decay (NMD). In addition, a deep intron mutation (c.125-47 C&gt;A) was detected in the\n                      <jats:italic toggle=\"yes\">GLI3<\/jats:italic>\n                      gene from the sporadic case, however, both bioinformatics analysis (HSF, splice AI, and CBS) and RT-PCR indicated that the variant c.125-47 C&gt;A had minimal if any impact on splicing of the\n                      <jats:italic toggle=\"yes\">GLI3<\/jats:italic>\n                      gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Two newly identified heterozygous frameshift mutations in the\n                      <jats:italic toggle=\"yes\">GLI3<\/jats:italic>\n                      gene were detected in two families with non-syndromic polydactyly, further extending the mutational spectrum of the\n                      <jats:italic toggle=\"yes\">GLI3<\/jats:italic>\n                      gene in non-syndromic polydactyly. Moreover, our study further expanded the phenotypic spectrum of non-syndromic polydactyly.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/gtmb.2023.0022","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T11:03:06Z","timestamp":1695898986000},"page":"299-305","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Two Novel Frameshift Mutations in the\n                    <i>GLI3<\/i>\n                    Gene Underlie Non-Syndromic Polydactyly in Chinese Families"],"prefix":"10.1177","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-4871","authenticated-orcid":false,"given":"Xiaoyan","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Fuzhou Second Hospital, Fuzhou, P.R. China."},{"name":"Department of Laboratory Medicine, Fuzhou Second Hospital of Xiamen University, School of Medicine, Xiamen University, Fuzhou, P.R. China."},{"name":"Department of Laboratory Medicine, The Third Clinical Medical College, Fujian Medical University, Fuzhou, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5783-7253","authenticated-orcid":false,"given":"Tengfei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Fuzhou Second Hospital, Fuzhou, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingrui","family":"Lin","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, The Affiliated People's Hospital of Fujian Traditional Medical University, Fuzhou, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Fuzhou Second Hospital, Fuzhou, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuancheng","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Fuzhou Second Hospital, Fuzhou, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2012.01866.x"},{"key":"e_1_3_4_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10779"},{"key":"e_1_3_4_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2011.02.007"},{"key":"e_1_3_4_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11832-007-0022-8"},{"key":"e_1_3_4_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.2.98"},{"key":"e_1_3_4_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.62"},{"key":"e_1_3_4_8_1","doi-asserted-by":"publisher","DOI":"10.1017\/erm.2015.18"},{"key":"e_1_3_4_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2005.00431.x"},{"key":"e_1_3_4_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/302070"},{"key":"e_1_3_4_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-092910-154048"},{"key":"e_1_3_4_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-012-0109-x"},{"key":"e_1_3_4_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/429346"},{"key":"e_1_3_4_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.9.1769"},{"key":"e_1_3_4_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20103"},{"key":"e_1_3_4_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.6.441"},{"key":"e_1_3_4_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10397"},{"key":"e_1_3_4_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12276"},{"key":"e_1_3_4_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2007.00935.x"},{"key":"e_1_3_4_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.15.3.212"},{"key":"e_1_3_4_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200523675"},{"key":"e_1_3_4_22_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.108.087114"},{"issue":"3","key":"e_1_3_4_23_1","first-page":"597","article-title":"Mapping one form of autosomal dominant postaxial polydactyly type A to chromosome 7p15-q11.23 by linkage analysis","volume":"60","author":"Radhakrishna U","year":"1997","unstructured":"Radhakrishna U, , Blouin JL, , Mehenn H, et al. Mapping one form of autosomal dominant postaxial polydactyly type A to chromosome 7p15-q11.23 by linkage analysis. 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