{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:59:18Z","timestamp":1780981158623,"version":"3.54.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"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. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Familial hypercholesterolemia (FH) is a genetic disorder of lipid metabolism characterized by elevated plasma low-density lipoprotein resulting in cardiovascular disease (CVD). The harmful mutations of LDLR are the main cause of FH. Especially, there is no effective treatment options for homozygous FH (HoFH) patients. Numerous FH cases have been reported, but most mutations remain unvalidated and lack gene correction studies. The study aims to assess the pathogenicity of a novel mutation,\n                      <jats:italic>LDLR<\/jats:italic>\n                      c.331C&amp;gt;T (p.Gln111Ter), and seek its gene correction strategy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The study systematically evaluated a female HoFH patient and her family. Using CRISPR\/Cas9 technology, a Huh7 cell line carrying the point mutation was constructed. The impact of this mutation on LDLR protein expression was confirmed by qPCR, Western blot (WB), and immunofluorescence. A high-fidelity gene correction system targeting the\n                      <jats:italic>LDLR<\/jats:italic>\n                      c.331C&amp;gt;T point mutation was established based on the prime editing (PE) technology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The HoFH patient exhibited a biallelic\n                      <jats:italic>LDLR<\/jats:italic>\n                      mutation comprising an\n                      <jats:italic>LDLR<\/jats:italic>\n                      c.1693_1696 del GGCA inherited from her mather and a\n                      <jats:italic>de novo LDLR<\/jats:italic>\n                      c.331C&amp;gt;T (p.Gln111Ter) mutation.\n                      <jats:italic>In vitro<\/jats:italic>\n                      validation indicated that the mutation impaired normal LDLR protein expression, and the candidate gene editing system achieved approximately 98% correction efficiency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>LDLR<\/jats:italic>\n                      c.331C&amp;gt;T is a likely pathogenic mutation, which canbe precisely corrected by PE technology. The study expands the spectrum of likely pathogenic mutations in FH and holds promise for personalized, precise gene therapy through customized therapeutic systems, potentially alleviating or curing HoFH\u2014a current challenge in conventional clinical management.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1814798","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:28:23Z","timestamp":1780979303000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A de novo LDLR mutation in severe familial hypercholesterolemia: case report, functional characterization, and a personalized gene correction strategy exploration"],"prefix":"10.3389","volume":"13","author":[{"given":"Shuran","family":"Zhang","sequence":"first","affiliation":[{"name":"Medical Genetics Department of The First People's Hospital of Yunnan Province\/Affiliated Hospital of Kunming University of Science and Technology, Key Laboratory Reproductive Health and Birth Defects Prevention and Control in Western China, National Health Commission, Key Laboratory of Birth Defects and Genetic Diseases of Yan Province","place":["Kunming, Yunnan, China"]},{"name":"School of Medicinie, Kunming University of Science and Technology","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenming","family":"Huang","sequence":"additional","affiliation":[{"name":"Medical Genetics Department of The First People's Hospital of Yunnan Province\/Affiliated Hospital of Kunming University of Science and Technology, Key Laboratory Reproductive Health and Birth Defects Prevention and Control in Western China, National Health Commission, Key Laboratory of Birth Defects and Genetic Diseases of Yan Province","place":["Kunming, Yunnan, 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Province","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Chang","sequence":"additional","affiliation":[{"name":"Medical Genetics Department of The First People's Hospital of Yunnan Province\/Affiliated Hospital of Kunming University of Science and Technology, Key Laboratory Reproductive Health and Birth Defects Prevention and Control in Western China, National Health Commission, Key Laboratory of Birth Defects and Genetic Diseases of Yan Province","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baosheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Medical Genetics Department of The First People's Hospital of Yunnan Province\/Affiliated Hospital of Kunming University of Science and Technology, Key Laboratory Reproductive Health and Birth Defects Prevention and Control in Western China, National Health Commission, Key Laboratory of Birth Defects and Genetic Diseases of Yan Province","place":["Kunming, Yunnan, China"]},{"name":"School of Medicinie, Kunming University of Science and Technology","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinman","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical Genetics Department of The First People's Hospital of Yunnan Province\/Affiliated Hospital of Kunming University of Science and Technology, Key Laboratory Reproductive Health and Birth Defects Prevention and Control in Western China, National Health Commission, Key Laboratory of Birth Defects and Genetic Diseases of Yan Province","place":["Kunming, Yunnan, China"]},{"name":"School of Medicinie, Kunming University of Science and Technology","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chan","sequence":"additional","affiliation":[{"name":"Medical Genetics Department of The First People's Hospital of 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