{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:20:42Z","timestamp":1747182042913,"version":"3.40.5"},"reference-count":13,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A novel <jats:italic>COL3A1<\/jats:italic> variant was identified in a Japanese case of Ehlers\u2013Danlos syndrome type IV (EDS\u2010IV) with a characteristic \u201cMadonna\u201d face, fragile uterus, and easy bruising in addition to a history of cavernous sinus fistula. We confirmed variable diameters of collagen fibrils in the dermis and decrease in type 3 collagen production from cultured fibroblasts. Genomic DNA sequencing of the COL3A1 region and COL3A1 cDNA sequence expressing in cultured fibroblasts identified that a nucleotide variation at c.951+2T&gt;G on intron 14 leads to skipping of exon 14 in <jats:italic>COL3A1<\/jats:italic> cDNA. The novel variation in the splice site of <jats:italic>COL3A1<\/jats:italic> region g.IVS14+2T&gt;G was not listed in the EDS\u2010IV pathogenic genetic databases including Human Gene Mutation Database, ClinVar, and Leiden Open Variation Database. Using the whole genome sequence database of 8380 Japanese individuals reported by the Tohoku Medical Megabank Organization (ToMMo) cohort study, we also confirmed that <jats:italic>COL3A1<\/jats:italic> g.IVS14+2T&gt;G was not a common single nucleotide variation in the Japanese population, although 13 EDS\u2010related <jats:italic>COL3A1<\/jats:italic> variants were identified in the ToMMo database of 8380 Japanese individuals. These results demonstrated that our case of EDS\u2010IV was a result of the novel variation of COL3A1 g.IVS14+2T&gt;G. These statistical genetics approaches with the combination of the ToMMo database of 8380 Japanese individuals and pathogenic genetic databases are a useful method to confirm the uniqueness of novel variation in Japanese.<\/jats:p>","DOI":"10.1111\/1346-8138.16131","type":"journal-article","created":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T07:07:59Z","timestamp":1630134479000},"page":"1918-1922","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ehlers\u2013Danlos syndrome type IV with a novel <i>COL3A1<\/i> exon 14 skipping variation confirmed by Tohoku Medical Megabank Organization genomic database"],"prefix":"10.1111","volume":"48","author":[{"given":"Kosuke","family":"Shido","sequence":"first","affiliation":[{"name":"Department of Dermatology Tohoku University Graduate School of Medicine Sendai Miyagi Japan"},{"name":"Tohoku Medical Megabank Organization Tohoku University Sendai Miyagi 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