{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:15:31Z","timestamp":1779196531252,"version":"3.51.4"},"reference-count":20,"publisher":"American Society for Clinical Investigation","issue":"6","funder":[{"name":"JSPS KAKENHI","award":["JP15K09738"],"award-info":[{"award-number":["JP15K09738"]}]},{"DOI":"10.13039\/501100008670","name":"Terumo Foundation for Life Sciences and Arts","doi-asserted-by":"crossref","award":["16-II 330"],"award-info":[{"award-number":["16-II 330"]}],"id":[{"id":"10.13039\/501100008670","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Northern Advancement Center for Science & Technology (NOASTEC) Foundation","award":["H28 T-1-42"],"award-info":[{"award-number":["H28 T-1-42"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,3,22]]},"abstract":"<jats:p>\n                    Heterozygous chromosomal inversions suppress recombination. Therefore, they may potentially influence recombination-associated phenotypes of human diseases, but no studies have verified this hypothesis. Here, we describe a 35-year-old man with severe congenital ichthyosis. Mutation analysis revealed a heterozygous splice-site mutation, c.1374-2A&gt;G (p.Ser458Argfs*120), in\n                    <jats:italic>KRT10<\/jats:italic>\n                    on 17q21.2. This mutation was previously reported in patients with ichthyosis with confetti type I (IWC-I), a prominent skin disease characterized by the frequent occurrence of recombination-induced reversion of pathogenic mutations. Intriguingly, the number of revertant skin areas in this patient is considerably reduced compared with typical IWC-I cases. G-banded karyotyping revealed that the patient harbors a heterozygous nonpathogenic inversion, inv(17)(p13q12), whose long-arm breakpoint was subsequently refined to chromosomal positions (chr17: 36,544,407\u201336,639,830) via FISH. Collectively, the only chance of revertant mosaicism through somatic recombination appears to involve recombination between the\n                    <jats:italic>KRT10<\/jats:italic>\n                    mutation and the inversion breakpoint. Indeed, in the examined revertant spot, the\n                    <jats:italic>KRT10<\/jats:italic>\n                    mutation was diminished by somatic recombination starting from chromosomal positions (chr17: 36,915,505\u201337,060,285) on 17q12. This study provides the first evidence to our knowledge implicating chromosomal inversions as a potential modifier of clinical phenotypes. Furthermore, the reduced occurrence of revertant spots in the recombination-suppressed patient suggests that somatic recombination is the main mechanism of revertant mosaicism in IWC-I.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.97595","type":"journal-article","created":{"date-parts":[[2018,3,21]],"date-time":"2018-03-21T11:01:17Z","timestamp":1521630077000},"source":"Crossref","is-referenced-by-count":12,"title":["Chromosomal inversions as a hidden disease-modifying factor for somatic recombination phenotypes"],"prefix":"10.1172","volume":"3","author":[{"given":"Toshifumi","family":"Nomura","sequence":"first","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shotaro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshinari","family":"Miyauchi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masae","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Shinkuma","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyuki","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"Nishie","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5863-9315","authenticated-orcid":true,"given":"Masashi","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, 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