{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T05:02:35Z","timestamp":1777006955669,"version":"3.51.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Split-hand\/foot malformation (SHFM) is a serious congenital anomaly. A multitude of pathogenic genes associated with SHFM have been identified;\n                      <jats:italic>TP63, DLX5, FGFR1<\/jats:italic>\n                      , and\n                      <jats:italic>WNT10B<\/jats:italic>\n                      are currently recognized. As a transcription factor, TP63 plays an important role in the development of the ectoderm.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified a pathogenic variant by extracting DNA from the peripheral blood of a patient with SHFM and performing whole-exome sequencing (WES). After verifying the variant through Sanger sequencing, a series of analytical procedures were conducted to determine its pathogenicity. These included conservative analysis, tolerance analysis of the mutant region, and three-dimensional molecular modeling of the protein.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A\n                      <jats:italic>TP63<\/jats:italic>\n                      frameshift mutation (NM_003722; c.2009_2010insA; p.N670Kfs\n                      <jats:sup>*<\/jats:sup>\n                      ) associated with SHFM was identified by WES and is predicted to cause a segmental deletion within the transactivation inhibitory domain (TID) of TP63. Bioinformatic analyses revealed that this locus is highly evolutionarily conserved and poorly tolerant of variation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We identified a\n                      <jats:italic>TP63<\/jats:italic>\n                      shift mutation in a patient with SHFM. This research contributes to the expansion of the spectrum of\n                      <jats:italic>TP63<\/jats:italic>\n                      variants and disease phenotypes, and is expected to provide valuable information for genetic counseling and prenatal diagnosis in families affected by similar congenital anomalies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1811133","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:31:05Z","timestamp":1777005065000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of novel tumor protein 63 variant associated with split-hand\/foot malformation and tooth agenesis"],"prefix":"10.3389","volume":"13","author":[{"given":"Jie-Yi","family":"Long","sequence":"first","affiliation":[{"name":"Department of Hand and Microsurgery, Xiangya Hospital, School of Life Sciences, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin-Zhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hand and Microsurgery, Xiangya Hospital, School of Life Sciences, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si-Hua","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Hand and Microsurgery, Xiangya Hospital, School of Life Sciences, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Run-Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hand and Microsurgery, Xiangya Hospital, School of Life Sciences, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie-Yuan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Hand and Microsurgery, Xiangya Hospital, School of Life Sciences, Central South University","place":["Changsha, China"]},{"name":"School of Medicine, Shaoxing University","place":["Shaoxing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Physical Education Institute, Hunan University of Financial and Economic","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen-Bo","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Hunan Normal University, Changsha","place":["Hunan, 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