{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:58Z","timestamp":1753869718206,"version":"3.41.2"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"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":["82172011"],"award-info":[{"award-number":["82172011"]}],"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; Gen Med"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary multiple exostosis (HME) is an autosomal dominant skeletal disorder characterized by the development of multiple cartilage\u2010covered tumors on the external surfaces of bones (osteochondromas). Most of HME cases result from heterozygous loss\u2010of\u2010function mutations in <jats:italic>EXT1<\/jats:italic> or <jats:italic>EXT2<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical examination was performed to diagnose the patients: Whole exome sequencing (WES) was used to identify pathogenic mutations in the proband, which is confirmed by Sanger sequencing and co\u2010segregation analysis: qRT\u2010PCR was performed to identify the mRNA expression level of <jats:italic>EXT1<\/jats:italic> in patient peripheral blood samples: minigene splicing assay was performed to mimic the splicing process of <jats:italic>EXT1<\/jats:italic> variants in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We evaluated the pathogenicity of <jats:italic>EXT1<\/jats:italic> c.1056\u00a0+\u00a01G\u00a0&gt;\u00a0T in a Chinese family with HME. The clinical, phenotypic, and genetic characterization of patients in this family were described. The variant was detected by whole\u2010exome sequencing (WES) and confirmed by Sanger sequencing. Sequencing of the RT\u2010PCR products from the patient's blood sample identified a large deletion (94 nucleotides), which is the whole exome 2 of the <jats:italic>EXT1<\/jats:italic> cDNA. Splicing assay indicated that the mutated minigene produced alternatively spliced transcripts, which cause a frameshift resulting in an early termination of protein expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study establishes the pathogenesis of the splicing mutation <jats:italic>EXT1<\/jats:italic> c.1056\u00a0+\u00a01G\u00a0&gt;\u00a0T to HME and provides scientific foundation for accurate diagnosis and precise medical intervention for HME.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1878","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T06:29:13Z","timestamp":1643783353000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic and functional analyses detect an <i>EXT1<\/i> splicing pathogenic variant in a Chinese hereditary multiple exostosis (<scp>HME<\/scp>) family"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4731-2186","authenticated-orcid":false,"given":"Jianwei","family":"Li","sequence":"first","affiliation":[{"name":"The Second Hospital Shanxi Medical University  Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Lvliang People\u2019s Hospital Shanxi Medical University  Lvliang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6340-6225","authenticated-orcid":false,"given":"Yaxin","family":"Han","sequence":"additional","affiliation":[{"name":"The First Hospital Shanxi Medical University  Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengfang","family":"Jin","sequence":"additional","affiliation":[{"name":"Lvliang People\u2019s Hospital Shanxi Medical University  Lvliang 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