{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:00:22Z","timestamp":1791140422685,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870474"],"award-info":[{"award-number":["81870474"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31601035"],"award-info":[{"award-number":["31601035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Split hand\/foot malformation (SHFM) is a congenital limb developmental disorder, which impairs the fine activities of hand\/foot in the affected individuals seriously. SHFM is commonly inherited as an autosomal dominant disease with incomplete penetrance. Chromosomal aberrations such as copy number variations and translocations have been linked to SHFM. This study aimed to identify the genetic cause for three patients with bilateral hand and foot malformation in a Chinese family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Karyotyping, single\u2010nucleotide polymorphism (SNP) array, whole exome sequencing, whole genome sequencing, and Sanger sequencing were applied to identify the pathogenic variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Karyotyping revealed that the three patients had balanced reciprocal translocation, 46, XX, t(3;15) (q29;q22). SNP array identified no pathogenic copy number variation in the proband. Trio\u2010WES (fetus\u2013mother\u2013father) sequencing results revealed no pathogenic variants in the genes related to SHFM. Whole\u2010genome low\u2010coverage mate\u2010pair sequencing (WGL\u2010MPS), breakpoint PCR, and Sanger sequencing identified the breakpoints disrupting <jats:italic>TP63<\/jats:italic> in the patients, but not in healthy family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study firstly reports that a translocation breakpoint disrupting <jats:italic>TP<\/jats:italic>63 contributes to the SHFM in a Chinese family, which expands our knowledge of genetic risk and counseling underlying SHFM. It provides a basis for genetic counseling and prenatal diagnosis (preimplantation genetic diagnosis) for this family.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1604","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T19:26:37Z","timestamp":1611170797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Whole genome sequencing reveals translocation breakpoints disrupting <i>TP63<\/i> gene underlying split hand\/foot malformation in a Chinese family"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0602-6063","authenticated-orcid":false,"given":"Ying","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Medical Genetics National Health Commission Key Laboratory of Birth Defects Research Hunan Provincial Maternal and Child Health Care Hospital Changsha 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