{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:52:07Z","timestamp":1792252327700,"version":"4.4.0"},"reference-count":30,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,18]],"date-time":"2020-10-18T00:00:00Z","timestamp":1602979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Keratinopathic ichthyoses (KI) are a clinically heterogeneous group of keratinization disorders due to mutations in KRT1, KTR10, or KRT2 genes encoding keratins of suprabasal epidermis. Characteristic clinical features include superficial blisters and erosions in infancy and progressive development of hyperkeratosis. Histopathology shows epidermolytic hyperkeratosis. We describe the clinical, histopathological, and molecular findings of a series of 26 Italian patients from 19 unrelated families affected with (i) epidermolytic ichthyosis due to KRT1 or KRT10 mutations (7 and 9 cases, respectively); (ii) KTR10-mutated ichthyosis with confetti (2 cases); (iii) KRT2-mutated superficial epidermolytic ichthyosis (5 cases); and (iv) KRT10-mutated epidermolytic nevus (2 cases). Of note, molecular genetic testing in a third case of extensive epidermolytic nevus revealed a somatic missense mutation (p.Asn186Asp) in the KRT2 gene, detected in DNA from lesional skin at an allelic frequency of 25% and, at very low frequency (1.5%), also in blood. Finally, we report three novel dominant mutations, including a frameshift mutation altering the C-terminal V2 domain of keratin 1 in three familiar cases presenting a mild phenotype. Overall, our findings expand the phenotypic and molecular spectrum of KI and show for the first time that epidermolytic nevus can be due to somatic KRT2 mutation.<\/jats:p>","DOI":"10.3390\/ijms21207707","type":"journal-article","created":{"date-parts":[[2020,10,18]],"date-time":"2020-10-18T21:26:06Z","timestamp":1603056366000},"page":"7707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0879-9825","authenticated-orcid":false,"given":"Andrea","family":"Diociaiuti","sequence":"first","affiliation":[{"name":"Dermatology Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza S. Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3501-6742","authenticated-orcid":false,"given":"Daniele","family":"Castiglia","sequence":"additional","affiliation":[{"name":"IDI-IRCCS, Via dei Monti di Creta, 104, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4158-5717","authenticated-orcid":false,"given":"Marialuisa","family":"Corbeddu","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza S. Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0722-9898","authenticated-orcid":false,"given":"Roberta","family":"Rotunno","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza S. Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Rossi","sequence":"additional","affiliation":[{"name":"Pathology Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza S. Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Pisaneschi","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza S. Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cesario","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza S. Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1502-5852","authenticated-orcid":false,"given":"Angelo Giuseppe","family":"Condorelli","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza S. Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Zambruno","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza S. Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"El Hachem","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza S. Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jaad.2009.11.020","article-title":"Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sor\u00e8ze 2009","volume":"63","author":"Oji","year":"2010","journal-title":"J. Am. Acad. Derm."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Has, C., Bauer, J.W., Bodemer, C., Bolling, M.C., Bruckner-Tuderman, L., Diem, A., Fine, J.D., Heagerty, A., Hovnanian, A., and Marinkovich, M.P. (2020). Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br. J. Derm.","DOI":"10.1111\/bjd.18921"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s40257-017-0313-x","article-title":"Inherited nonsyndromic ichthyoses: An update on pathophysiology, diagnosis and treatment","volume":"19","author":"Vahlquist","year":"2018","journal-title":"Am. J. Clin. Derm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1093\/hmg\/ddl028","article-title":"A human keratin 10 knockout causes recessive epidermolytic hyperkeratosis","volume":"15","author":"Huber","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1111\/j.1365-2133.2010.09665.x","article-title":"Lethal autosomal recessive epidermolytic ichthyosis due to a novel donor splice-site mutation in KRT10","volume":"162","author":"Covaciu","year":"2010","journal-title":"Br. J. Derm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1038\/sj.jid.5701257","article-title":"Mild recessive bullous congenital ichthyosiform erythroderma due to a previously unidentified homozygous keratin 10 nonsense mutation","volume":"128","author":"Tsubota","year":"2008","journal-title":"J. Investig. Derm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/j.1365-2133.2010.10096.x","article-title":"Expanding the keratin mutation database: Novel and recurrent mutations and genotype-phenotype correlations in 28 patients with epidermolytic ichthyosis","volume":"164","author":"Arin","year":"2011","journal-title":"Br. J. Derm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s13023-015-0336-4","article-title":"Ichthyosis with confetti: Clinics, molecular genetics and management","volume":"10","author":"Guerra","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1365-2133.1990.tb08292.x","article-title":"Epidermolytic hyperkeratosis: Generalized form in children from parents with systematized linear form","volume":"122","author":"Nazzaro","year":"1990","journal-title":"Br. J. Derm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1056\/NEJM199411243312103","article-title":"Genetic and clinical mosaicism in a type of epidermal nevus","volume":"331","author":"Paller","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1038\/sj.jid.5700553","article-title":"Generalized epidermolytic hyperkeratosis in two unrelated children from parents with localized linear form, and prenatal diagnosis","volume":"126","author":"Chassaing","year":"2006","journal-title":"J. Investig. Derm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/sj.jid.5700712","article-title":"Keratin 1 gene mutation detected in epidermal nevus with epidermolytic hyperkeratosis","volume":"127","author":"Tsubota","year":"2007","journal-title":"J. Investig. Derm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1016\/j.jid.2017.04.036","article-title":"A Child with epidermolytic ichthyosis from a parent with epidermolytic nevus: Risk evaluation of transmission from mosaic to germline","volume":"137","author":"Kono","year":"2017","journal-title":"J. Investig. Derm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jaad.2008.02.031","article-title":"Histopathologic characterization of epidermolytic hyperkeratosis: A systematic review of histology from the national registry for ichthyosis and related skin disorders","volume":"59","author":"Ross","year":"2008","journal-title":"J. Am. Acad. Derm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13023-016-0384-4","article-title":"Role of molecular testing in the multidisciplinary diagnostic approach of ichthyosis","volume":"11","author":"Diociaiuti","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"473","DOI":"10.2340\/00015555-2299","article-title":"Expanding the clinical and genetic spectrum of KRT1, KRT2 and KRT10 mutations in keratinopathic ichthyosis","volume":"96","author":"Hotz","year":"2016","journal-title":"Acta Derm. Venereol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1046\/j.1523-1747.2003.12084.x","article-title":"Epidermolytic hyperkeratosis and epidermolysis bullosa simplex caused by frameshift mutations altering the v2 tail domains of keratin 1 and keratin 5","volume":"120","author":"Sprecher","year":"2003","journal-title":"J. Investig. Derm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/j.1468-3083.2009.03175.x","article-title":"Mutation L437P in the 2B domain of keratin 1 causes diffuse palmoplantar keratoderma in a Chinese pedigree","volume":"23","author":"Liu","year":"2009","journal-title":"J. Eur. Acad. Derm. Venereol."},{"key":"ref_19","first-page":"179","article-title":"Preferential sites in keratin 10 that are mutated in epidermolytic hyperkeratosis","volume":"54","author":"Chipev","year":"1994","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1046\/j.1523-1747.2000.00817.x","article-title":"A novel asparagine-->aspartic acid mutation in the rod 1A domain in keratin 2e in a Japanese family with ichthyosis bullosa of Siemens","volume":"114","author":"Takizawa","year":"2000","journal-title":"J. Investig. Derm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"579","DOI":"10.2340\/00015555-1796","article-title":"Early immunopathological diagnosis of ichthyosis with confetti in two sporadic cases with new mutations in keratin 10","volume":"94","author":"Diociaiuti","year":"2014","journal-title":"Acta Derm. Venereol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1046\/j.1523-1747.2003.12534.x","article-title":"Splice site and deletion mutations in keratin (KRT1 and KRT10) genes: Unusual phenotypic alterations in Scandinavian patients with epidermolytic hyperkeratosis","volume":"121","author":"Virtanen","year":"2003","journal-title":"J. Investig. Derm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1001\/archderm.1994.01690080092014","article-title":"Clinical heterogeneity in epidermolytic hyperkeratosis","volume":"130","author":"DiGiovanna","year":"1994","journal-title":"Arch. Derm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"309","DOI":"10.2340\/00015555-1447","article-title":"Generalized and naevoid epidermolytic ichthyosis in Denmark: Clinical and mutational findings","volume":"93","author":"Bygum","year":"2013","journal-title":"Acta Derm. Venereol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hinbest, A.J., Eldirany, S.A., Ho, M., and Bunick, C.G. (2020). Molecular modeling of pathogenic mutations in the keratin 1B domain. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186641"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1111\/j.1365-2133.2005.06598.x","article-title":"Ichthyosis bullosa of Siemens: Its correct diagnosis facilitated by molecular genetic testing","volume":"152","author":"Akiyama","year":"2005","journal-title":"Br. J. Derm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1046\/j.1365-2133.1999.02772.x","article-title":"Ichthyosis bullosa of Siemens: Report of a family with evidence of a keratin 2e mutation, and a review of the literature","volume":"140","author":"Basarab","year":"1999","journal-title":"Br. J. Derm."},{"key":"ref_28","first-page":"e346","article-title":"Superficial epidermolytic ichthyosis-Hypertrichosis as a clue to diagnosis","volume":"33","author":"Gameiro","year":"2016","journal-title":"Pediatr. Derm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1111\/jdv.15613","article-title":"Burden of itch in ichthyosis: A multicentre study in 94 patients","volume":"33","author":"Giehl","year":"2019","journal-title":"J. Eur. Acad. Derm. Venereol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: The human genomic variant search engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/20\/7707\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:23:31Z","timestamp":1760178211000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/20\/7707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,18]]},"references-count":30,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["ijms21207707"],"URL":"https:\/\/doi.org\/10.3390\/ijms21207707","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,18]]}}}