{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:25:10Z","timestamp":1781796310707,"version":"3.54.5"},"reference-count":21,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Incontinentia pigmenti (IP) is a rare X\u2010linked disorder affecting the skin and other ectodermal tissues that is caused by mutation of the <jats:italic>IKBKG<\/jats:italic>\/<jats:italic>NEMO<\/jats:italic> gene. Previous studies have reported that the overall mutation detection rate in IP is ~75%. We hypothesized that a low\u2010level mosaicism existed in the remaining cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genomic variations in the <jats:italic>IKBKG<\/jats:italic> gene were examined in 30 IP probands and their family members. Standard mutational analyses were performed to detect common deletions, nucleotide alterations, and copy number variations. To assess skewing of the X chromosome inactivation (XCI) pattern, a HUMARA assay was performed. We compared the results of this analysis with phenotype severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pathogenic variants were identified in 20 probands (66.7%), the rate of detection was suboptimal. The remaining 10 probands tended to manifest a mild phenotype with no skewed X chromosome inactivation that is generally observed in IP patients. Quantitative nested PCR and digital droplet PCR were performed for the 10 patients and mosaicism of the common <jats:italic>IKBKG<\/jats:italic> deletion were identified in five patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, we detected 25 <jats:italic>IKBKG<\/jats:italic> mutations (83.3%). Determination of the XCI value in advance of mutational analyses for IP could improve the mutation detection rate. Our improved detection rate for these mutations, particularly those with a low\u2010level mosaicism, may present opportunities for appropriate genetic counseling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1531","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T15:54:17Z","timestamp":1603295657000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Molecular analysis of low\u2010level mosaicism of the <i>IKBKG<\/i> mutation using the X Chromosome Inactivation pattern in Incontinentia Pigmenti"],"prefix":"10.1002","volume":"8","author":[{"given":"Miki","family":"Kawai","sequence":"first","affiliation":[{"name":"Division of Molecular Genetics Institute for Comprehensive Medical Science Fujita Health University Toyoake Japan"},{"name":"Department of Clinical Genetics Fujita Health University Hospital Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takema","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics Institute for Comprehensive Medical Science Fujita Health University Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics Institute for Comprehensive Medical Science Fujita Health University Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Shinkai","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics Institute for Comprehensive Medical Science Fujita Health University Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehito","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics Institute for Comprehensive Medical Science Fujita Health University Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5690-5218","authenticated-orcid":false,"given":"Hiroki","family":"Kurahashi","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics Institute for Comprehensive Medical Science Fujita Health University Toyoake Japan"},{"name":"Department of Clinical Genetics Fujita Health University Hospital Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.22.2557"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/318806"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10150"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/346119"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2011.05.003"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI124011"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22483"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/85837"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh192"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2006.09.019"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21069"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20109\u201093"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr556"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20739"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20100004.2004.00310.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09814"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.30.1.53"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.016"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12223"},{"key":"e_1_2_9_21_1","unstructured":"Orphanet. 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