{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:56:00Z","timestamp":1753869360877,"version":"3.41.2"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary multiple exostoses (HME), also referred to as multiple osteochondromas, is an autosomal dominant skeletal disease characterized by the development of multiple overgrown benign bony tumors capped by cartilage and is associated with bone deformity, joint limitation, and short stature. Mutations in exostosin glycosyltransferase (<jats:italic>EXT<\/jats:italic>)1 and <jats:italic>EXT2<\/jats:italic> genes, which are located on chromosomes 8q24.1 and 11p13, contribute to the pathogenesis of HME.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the present study, a genetic analysis of a four\u2010generation Chinese family with HME was conducted using whole\u2010exome sequencing (WES), followed by validation using Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel heterozygous frameshift mutation in exon 5 of <jats:italic>EXT2<\/jats:italic> (c.944dupT, p.Leu316fs) was identified in all affected individuals but was not detected in any unaffected individuals. This mutation results in a frameshift that introduces a premature termination codon at position 318 (p.Leu316fs) with the ability to produce a truncated EXT2 protein that lacks the last 433 amino acids at its C\u2010terminal to indicate a defective exostosin domain and the absence of the glycosyltransferase family 64 domain, or to lead to the degradation of mRNAs by nonsense\u2010mediated mRNA decay, which is critical for the function of <jats:italic>EXT2<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate that WES is effective in extending the <jats:italic>EXT<\/jats:italic> mutational spectra and is advantageous for genetic counseling and the subsequent prenatal diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.23968","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T19:21:01Z","timestamp":1629228061000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of a novel <i>EXT2<\/i> frameshift mutation in a family with hereditary multiple exostoses by whole\u2010exome sequencing"],"prefix":"10.1002","volume":"35","author":[{"given":"Mei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology West China Second University Hospital Sichuan University Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Ministry of Education Sichuan University Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanbing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; 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