{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:38:37Z","timestamp":1790764717071,"version":"4.1.0"},"reference-count":25,"publisher":"American Academy of Pediatrics (AAP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:p>Incontinentia pigmenti (IP; Online Mendelian Inheritance in Man catalog #308300) is an X-linked dominant ectodermal disorder caused by mutations of the inhibitor of \u03ba polypeptide gene enchancer in B cells, kinase \u03b3 (IKBKG)\/ nuclear factor \u03baB, essential modulator (NEMO) gene. Hemizygous IKBKG\/NEMO loss-of-function (LoF) mutations are lethal in males, thus patients are female, and the disease is always transmitted from an IP-affected mother to her daughter. We present 2 families with father-to-daughter transmission of IP and provide for the first time molecular evidence that the combination of somatic and germ-line mosaicism for IKBKG\/NEMO loss of function mutations in IP males resulted in the transmission of the disease to a female child. We searched for the IKBKG\/NEMO mutant allele in blood, urine, skin, and sperm DNA and found that the 2 fathers were somatic and germ-line mosaics for the p.Gln132\u00d7mutation or the exon 4\u201310 deletion of IKBKG\/NEMO, respectively. The highest level of IKBKG\/NEMO mutant cells was detected in the sperm, which might explain the recurrence of the disease. We therefore recommend careful clinical evaluation in IP male cases and the genetic investigation in sperm DNA to ensure correct genetic counseling and prevent the risk of paternal transmission of IP.<\/jats:p>","DOI":"10.1542\/peds.2016-2950","type":"journal-article","created":{"date-parts":[[2017,8,9]],"date-time":"2017-08-09T09:10:18Z","timestamp":1502269818000},"source":"Crossref","is-referenced-by-count":30,"title":["Unusual Father-to-Daughter Transmission of Incontinentia Pigmenti Due to Mosaicism in IP Males"],"prefix":"10.1542","volume":"140","author":[{"given":"Francesca","family":"Fusco","sequence":"first","affiliation":[{"name":"Institute of Genetics and Biophysics \u201cAdriano Buzzati-Traverso,\u201d IGB-CNR, Naples, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde Immacolata","family":"Conte","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics \u201cAdriano Buzzati-Traverso,\u201d IGB-CNR, Naples, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Diociaiuti","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Bambino Ges\u00f9 Children\u2019s Hospital\u2014IRCCS, Rome, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Bigoni","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Logistica of Medical Genetics, Ferrara University Hospital, Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francesca","family":"Branda","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics \u201cAdriano Buzzati-Traverso,\u201d IGB-CNR, Naples, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ferlini","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Logistica of Medical Genetics, Ferrara University Hospital, Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"El Hachem","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Bambino Ges\u00f9 Children\u2019s Hospital\u2014IRCCS, Rome, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde Valeria","family":"Ursini","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics \u201cAdriano Buzzati-Traverso,\u201d IGB-CNR, Naples, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2017,9,1]]},"reference":[{"key":"2021121014495734800_B1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1750-1172-8-25","article-title":"Systematic review of central nervous system anomalies in incontinentia pigmenti.","volume":"8","author":"Mini\u0107","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"2021121014495734800_B2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/1750-1172-9-93","article-title":"Incontinentia pigmenti: report on data from 2000 to 2013.","volume":"9","author":"Fusco","year":"2014","journal-title":"Orphanet J Rare Dis"},{"key":"2021121014495734800_B3","volume-title":"GeneReviews\u00ae","author":"Scheuerle","year":"1993"},{"issue":"2","key":"2021121014495734800_B4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1067\/mjd.2002.125949","article-title":"Incontinentia pigmenti: a review and update on the molecular basis of pathophysiology.","volume":"47","author":"Berlin","year":"2002","journal-title":"J Am Acad Dermatol"},{"issue":"1","key":"2021121014495734800_B5","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1136\/jmg.30.1.53","article-title":"Incontinentia pigmenti (Bloch-Sulzberger syndrome).","volume":"30","author":"Landy","year":"1993","journal-title":"J Med Genet"},{"issue":"6","key":"2021121014495734800_B6","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1111\/cge.12223","article-title":"Incontinentia pigmenti diagnostic criteria update.","volume":"85","author":"Mini\u0107","year":"2014","journal-title":"Clin Genet"},{"issue":"6785","key":"2021121014495734800_B7","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/35013114","article-title":"Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti.","volume":"405","author":"Smahi","year":"2000","journal-title":"Nature"},{"issue":"3","key":"2021121014495734800_B8","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.gde.2006.04.013","article-title":"NEMO, NFkappaB signaling and incontinentia pigmenti.","volume":"16","author":"Nelson","year":"2006","journal-title":"Curr Opin Genet Dev"},{"issue":"18","key":"2021121014495734800_B9","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1101\/gad.1228704","article-title":"Signaling to NF-kappaB.","volume":"18","author":"Hayden","year":"2004","journal-title":"Genes Dev"},{"issue":"6","key":"2021121014495734800_B10","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1093\/hmg\/ddr556","article-title":"Genomic architecture at the Incontinentia Pigmenti locus favours de novo pathological alleles through different mechanisms.","volume":"21","author":"Fusco","year":"2012","journal-title":"Hum Mol Genet"},{"issue":"2","key":"2021121014495734800_B11","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/humu.22483","article-title":"Insight into IKBKG\/NEMO locus: report of new mutations and complex genomic rearrangements leading to incontinentia pigmenti disease.","volume":"35","author":"Conte","year":"2014","journal-title":"Hum Mutat"},{"issue":"9","key":"2021121014495734800_B12","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1002\/humu.21069","article-title":"Microdeletion\/duplication at the Xq28 IP locus causes a de novo IKBKG\/NEMO\/IKKgamma exon4_10 deletion in families with incontinentia pigmenti.","volume":"30","author":"Fusco","year":"2009","journal-title":"Hum Mutat"},{"issue":"10","key":"2021121014495734800_B13","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S1471-4914(01)02154-2","article-title":"NEMO\/IKK gamma: linking NF-kappa B to human disease.","volume":"7","author":"Courtois","year":"2001","journal-title":"Trends Mol Med"},{"issue":"3","key":"2021121014495734800_B14","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/(SICI)1096-8628(19980518)77:3<201::AID-AJMG5>3.0.CO;2-S","article-title":"Male cases of incontinentia pigmenti: case report and review.","volume":"77","author":"Scheuerle","year":"1998","journal-title":"Am J Med Genet"},{"issue":"2","key":"2021121014495734800_B15","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jaad.2006.09.019","article-title":"Clinical diagnosis of incontinentia pigmenti in a cohort of male patients.","volume":"56","author":"Fusco","year":"2007","journal-title":"J Am Acad Dermatol"},{"issue":"7","key":"2021121014495734800_B16","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1002\/ajmg.a.37004","article-title":"Somatic mosaicism of a novel IKBKG mutation in a male patient with incontinentia pigmenti.","volume":"167","author":"Hull","year":"2015","journal-title":"Am J Med Genet A"},{"issue":"6","key":"2021121014495734800_B17","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1086\/324591","article-title":"Survival of male patients with incontinentia pigmenti carrying a lethal mutation can be explained by somatic mosaicism or Klinefelter syndrome.","volume":"69","author":"Kenwrick","year":"2001","journal-title":"Am J Hum Genet"},{"issue":"5","key":"2021121014495734800_B18","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1111\/bjd.14615","article-title":"Incontinentia pigmenti in a father and daughter.","volume":"175","author":"Rashidghamat","year":"2016","journal-title":"Br J Dermatol"},{"issue":"3","key":"2021121014495734800_B19","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1002\/ajmg.1320170316","article-title":"Incontinentia pigmenti in a father and his daughter.","volume":"17","author":"Sommer","year":"1984","journal-title":"Am J Med Genet"},{"issue":"2 Pt 2","key":"2021121014495734800_B20","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/0190-9622(93)70198-3","article-title":"Incontinentia pigmenti: transmission from father to daughter.","volume":"29","author":"Emery","year":"1993","journal-title":"J Am Acad Dermatol"},{"issue":"11","key":"2021121014495734800_B21","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1136\/jmg.32.11.887","article-title":"Gonadal mosaicism for incontinentia pigmenti in a healthy male.","volume":"32","author":"Kirchman","year":"1995","journal-title":"J Med Genet"},{"issue":"7","key":"2021121014495734800_B22","doi-asserted-by":"crossref","DOI":"10.1038\/ejhg.2012.227","article-title":"Clinical Utility Gene Card for: incontinentia pigmenti.","volume":"21","author":"Fusco","year":"2013","journal-title":"Eur J Hum Genet"},{"issue":"1","key":"2021121014495734800_B23","doi-asserted-by":"crossref","first-page":"519","DOI":"10.4238\/vol10-1gmr1055","article-title":"A simplified universal genomic DNA extraction protocol suitable for PCR.","volume":"10","author":"Wang","year":"2011","journal-title":"Genet Mol Res"},{"key":"2021121014495734800_B24","doi-asserted-by":"crossref","DOI":"10.1002\/0471142727.mb0213s98","article-title":"Preparation of genomic DNA from mammalian sperm.","author":"Weyrich","year":"2012","journal-title":"Curr Protoc Mol Biol"},{"issue":"2","key":"2021121014495734800_B25","doi-asserted-by":"crossref","first-page":"216","DOI":"10.3390\/genes6020216","article-title":"Genetic mosaics and the germ line lineage.","volume":"6","author":"Samuels","year":"2015","journal-title":"Genes (Basel)"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/doi\/10.1542\/peds.2016-2950\/1104357\/peds_20162950.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/doi\/10.1542\/peds.2016-2950\/1104357\/peds_20162950.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T04:23:37Z","timestamp":1639196617000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/140\/3\/e20162950\/38356\/Unusual-Father-to-Daughter-Transmission-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,1]]},"references-count":25,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,9,1]]},"published-print":{"date-parts":[[2017,9,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2016-2950","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,1]]},"article-number":"e20162950"}}