{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:15:49Z","timestamp":1774685749798,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T00:00:00Z","timestamp":1549497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Samsung Medical Center","award":["#GFO217006"],"award-info":[{"award-number":["#GFO217006"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple osteochondromas (MOs) or hereditary multiple exostoses is a rare autosomal\u2010dominant disease characterized by growths of MOs, which are benign cartilage\u2010capped bone tumors that grow away from the growth plates. Almost 90% of MOs have a molecular explanation and 10% are unexplained. MOs are genetically heterogeneous with two causal genes on 8q24.11 (<jats:italic>EXT1<\/jats:italic>) and 11p12 (<jats:italic>EXT2<\/jats:italic>), with a higher frequency in <jats:italic>EXT1<\/jats:italic>. MO is a very rare genetic disorder, and the genotype\u2013phenotype of MO with <jats:italic>EXT2<\/jats:italic> mutation has not been well investigated in Korea. We present the clinical radiographic and molecular analysis of a four\u2010generation Korean family with 11 MO\u2010affected members (seven males and four females). The affected members from the third generation available for molecular analysis and their detailed medical histories showed moderate\u2010to\u2010severe phenotypes (clinical classes II\u2013III), including bony deformities and limb misalignment with pain requiring surgical correction. The x\u2010rays showed MOs in multiple sites. A novel <jats:italic>EXT2<\/jats:italic> frameshift mutation (c.590delC, p.P197Qfs*73) was revealed by targeted exome sequencing in the affected members of this family. In this article, we not only expand the phenotypic\u2013genotypic spectrum of MOs but also highlight the phenotypic heterogeneity in a family with the same mutation. In addition, we compiled the mutation spectrum of <jats:italic>EXT2<\/jats:italic> from a literature review and identified that exon 2 of <jats:italic>EXT2<\/jats:italic> is a mutation hot spot. Early medical attention with diagnosis of MO through careful examination of the clinical manifestations and genetic analysis can provide the opportunity to establish coordinated multispecialty management of the patient.<\/jats:p>","DOI":"10.1111\/ahg.12298","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T21:09:23Z","timestamp":1549573763000},"page":"160-170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of a novel mutation in <i>EXT2<\/i> in a fourth\u2010generation Korean family with multiple osteochondromas and overview of mutation spectrum"],"prefix":"10.1111","volume":"83","author":[{"given":"Aram","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinsup","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ja\u2010Hyun","family":"Jang","sequence":"additional","affiliation":[{"name":"Green Cross Genome  Yongin\u2010si Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, SAIHST Sungkyunkwan University  Seoul, Samsung Genome Institute, Samsung Medical Center Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji\u2010Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Inha University Hospital Inha University Graduate School of Medicine  Incheon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2913-059X","authenticated-orcid":false,"given":"Sung Yoon","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong\u2010Kyu","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,2,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00653.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/BLO.0b013e3181334b51"},{"key":"e_1_2_8_4_1","first-page":"110","article-title":"Hereditary 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