{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T13:38:04Z","timestamp":1770989884668,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T00:00:00Z","timestamp":1632528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Epidermolysis bullosa simplex is a disease that belongs to a group of genodermatoses characterised by the formation of superficial bullous lesions caused by minor mechanical trauma to the skin. The skin fragility observed in the EBS is mainly caused by pathogenic variants in the KRT5 and KRT14 genes that compromise the mechanical stability of epithelial cells. By performing DNA sequencing in a female patient with EBS, we found the pathogenic variant c.967G&gt;A (p.Val323Met) in the KRT5 gene. This variant co-segregated with EBS in the family pedigree and was transmitted in an autosomal dominant inheritance manner. This is the first report showing a familial form of EBS due to this pathogenic variant.<\/jats:p>","DOI":"10.3390\/genes12101503","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T04:55:33Z","timestamp":1632718533000},"page":"1503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Familial Form of Epidermolysis Bullosa Simplex Associated with a Pathogenic Variant in KRT5"],"prefix":"10.3390","volume":"12","author":[{"given":"Francesco","family":"Paduano","sequence":"first","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Tecnologica Research Institute and Marrelli Health, Biomedical Section, Stem Cells and Medical Genetics Units, 88900 Crotone, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5451-593X","authenticated-orcid":false,"given":"Emma","family":"Colao","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Grillone","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9233-0474","authenticated-orcid":false,"given":"Marco Flavio Michele","family":"Vismara","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosario","family":"Amato","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Nistic\u00f2","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5576-4946","authenticated-orcid":false,"given":"Chiara","family":"Mignogna","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Dastoli","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda","family":"Fabiani","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossella","family":"Zucco","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Trapasso","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Experimental and Clinical Medicine, Campus S. Venuta, University Magna Graecia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Perrotti","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8524-7402","authenticated-orcid":false,"given":"Rodolfo","family":"Iuliano","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41572-020-0210-0","article-title":"Epidermolysis bullosa","volume":"6","author":"Bardhan","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.clindermatol.2011.03.012","article-title":"Inherited epidermolysis bullosa: New diagnostic criteria and classification","volume":"30","author":"Intong","year":"2012","journal-title":"Clin. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.0022-202X.2005.23818.x","article-title":"Epidermolysis bullosa simplex: Recurrent and de novo mutations in the KRT5 and KRT14 genes, phenotype\/genotype correlations, and implications for genetic counseling and prenatal diagnosis","volume":"125","author":"Pfendner","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.jaad.2014.01.903","article-title":"Inherited epidermolysis bullosa: Updated recommendations on diagnosis and classification","volume":"70","author":"Fine","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.abd.2020.05.001","article-title":"Inherited epidermolysis bullosa: Update on the clinical and genetic aspects\u2606,\u2606\u2606","volume":"95","author":"Mariath","year":"2020","journal-title":"An. Bras. De Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/bjd.18921","article-title":"Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility","volume":"183","author":"Has","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1172\/JCI38177","article-title":"Epidermolysis bullosa simplex: A paradigm for disorders of tissue fragility","volume":"119","author":"Coulombe","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/0092-8674(80)90094-X","article-title":"Changes in keratin gene expression during terminal differentiation of the keratinocyte","volume":"19","author":"Fuchs","year":"1980","journal-title":"Cell"},{"key":"ref_9","first-page":"32","article-title":"A novel mutation in the L12 domain of keratin 5 in the K\u00f6bner variant of epidermolysis bullosa simplex","volume":"23","author":"Hsu","year":"2005","journal-title":"Dermatol. Sin."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1177\/0394632016650895","article-title":"Inflammation and macrophage polarization in cutaneous melanoma: Histopathological and immunohistochemical study","volume":"29","author":"Scali","year":"2016","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Paduano, F., Colao, E., Loddo, S., Orlando, V., Trapasso, F., Novelli, A., Perrotti, N., and Iuliano, R. (2020). 7q35 microdeletion and 15q13. 3 and xp22. 33 microduplications in a patient with severe myoclonic epilepsy, microcephaly, dysmorphisms, severe psychomotor delay and intellectual disability. Genes, 11.","DOI":"10.3390\/genes11050525"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Paduano, F., Fabiani, F., Colao, E., Trapasso, F., Perrotti, N., Barbieri, V., Baudi, F., and Iuliano, R. (2021). Case Report: Identification of a Novel Pathogenic Germline TP53 Variant in a Family With Li\u2013Fraumeni Syndrome. Front. Genet., 1541.","DOI":"10.3389\/fgene.2021.734809"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1002\/humu.9124","article-title":"Mutation analysis of the entire keratin 5 and 14 genes in patients with epidermolysis bullosa simplex and identification of novel mutations","volume":"21","author":"Vlies","year":"2003","journal-title":"Hum. Mutat."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Patel, P.M., Jones, V.A., Behnam, C.T., Zenzo, G.D., and Amber, K.T. (2021). A Review of Acquired Autoimmune Blistering Diseases in Inherited Epidermolysis Bullosa: Implications for the Future of Gene Therapy. Antibodies, 10.","DOI":"10.3390\/antib10020019"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/humu.20652","article-title":"The Human Intermediate Filament Database: Comprehensive information on a gene family involved in many human diseases","volume":"29","author":"Szeverenyi","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bendl, J., Stourac, J., Salanda, O., Pavelka, A., Wieben, E.D., Zendulka, J., Brezovsky, J., and Damborsky, J. (2014). PredictSNP: Robust and accurate consensus classifier for prediction of disease-related mutations. PLoS Comput. Biol., 10.","DOI":"10.1371\/journal.pcbi.1003440"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1046\/j.1523-1747.1998.00308.x","article-title":"A novel mutation in the L12 domain of keratin 5 in the K\u00f6bner variant of epidermolysis bullosa simplex","volume":"111","author":"Galligan","year":"1998","journal-title":"J. Investig. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.2340\/00015555-2715","article-title":"A review of 52 pedigrees with epidermolysis bullosa simplex identifying ten novel mutations in KRT5 and KRT14 in Australia","volume":"97","author":"Kim","year":"2017","journal-title":"Acta Derm.-Venereol."},{"key":"ref_21","first-page":"637","article-title":"Mutations in KRT5 and KRT14 cause epidermolysis bullosa simplex in 75% of the patients","volume":"164","author":"Bolling","year":"2011","journal-title":"Br. J. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/jid.2011.450","article-title":"Defining keratin protein function in skin epithelia: Epidermolysis bullosa simplex and its aftermath","volume":"132","author":"Coulombe","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s13353-015-0310-9","article-title":"Novel sporadic and recurrent mutations in KRT5 and KRT14 genes in Polish epidermolysis bullosa simplex patients: Further insights into epidemiology and genotype\u2013phenotype correlation","volume":"57","author":"Giza","year":"2016","journal-title":"J. Appl. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/sj.jid.5700571","article-title":"Epidermolysis bullosa simplex in Scotland caused by a spectrum of keratin mutations","volume":"127","author":"Rugg","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Foley, C., Moran, B., Sweeney, K., and Watson, R. (2013). Cardiac arrest and dilated cardiomyopathy in a patient with epidermolysis bullosa simplex and hidradenitis suppurativa: P6480. J. Am. Acad. Dermatol., 68.","DOI":"10.1016\/j.jaad.2012.12.189"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/bjd.16897","article-title":"Epidermolysis bullosa simplex generalized severe induces a T helper 17 response and is improved by apremilast treatment","volume":"180","author":"Castela","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Scala, E., Cacciapuoti, S., Garzorz-Stark, N., Megna, M., Marasca, C., Seiringer, P., Volz, T., Eyerich, K., and Fabbrocini, G. (2021). Hidradenitis Suppurativa: Where We Are and Where We Are Going. Cells, 10.","DOI":"10.3390\/cells10082094"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Annicchiarico, G., Morgese, M.G., Esposito, S., Lopalco, G., Lattarulo, M., Tampoia, M., Bonamonte, D., Brunetti, L., Vitale, A., and Lapadula, G. (2015). Proinflammatory cytokines and antiskin autoantibodies in patients with inherited epidermolysis bullosa. Medicine, 94.","DOI":"10.1097\/MD.0000000000001528"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/10\/1503\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:05:00Z","timestamp":1760166300000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/10\/1503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,25]]},"references-count":28,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["genes12101503"],"URL":"https:\/\/doi.org\/10.3390\/genes12101503","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,25]]}}}