{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T09:07:39Z","timestamp":1760346459774,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2015,9,9]],"date-time":"2015-09-09T00:00:00Z","timestamp":1441756800000},"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>Non-bullous congenital ichthyosiform erythroderma (NBCIE) is a hereditary disorder of keratinization caused by pathogenic variants in genes encoding enzymes important to lipid processing and terminal keratinocyte differentiation. Impaired function of these enzymes can cause pathologic epidermal scaling, significantly reduced skin barrier function. In this study, we have performed a focused, genetic analysis of a probrand affected by NBCIE and extended this to his consanguineous parents. Targeted capture and next-generation sequencing was performed on NBCIE associated genes in the proband and his unaffected consanguineous parents. We identified a homozygous nonsense variant c.814C&gt;T (p.Arg272*) in ALOXE3 (NM_001165960.1) in the proband and discovered that his parents are both heterozygous carriers of the variant. The clinical manifestations of the proband\u2019s skin were consistent with NBCIE, and detailed histopathological assessment revealed epidermal bulla formation and Majocchi\u2019s granuloma. Infection with Trichophyton rubrum was confirmed by culture. The patient responded to oral terbinafine antifungal treatment. Decreased skin barrier function, such as that caused by hereditary disorders of keratinization, can increase the risk of severe cutaneous fungal infections and the formation of Majocchi\u2019s granuloma and associated alopecia. Patients with NBCIE should be alerted to the possible predisposition for developing dermatophytoses and warrant close clinical follow-up.<\/jats:p>","DOI":"10.3390\/ijms160921791","type":"journal-article","created":{"date-parts":[[2015,9,9]],"date-time":"2015-09-09T13:16:18Z","timestamp":1441804578000},"page":"21791-21801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Homozygous ALOXE3 Nonsense Variant Identified in a Patient with Non-Bullous Congenital Ichthyosiform Erythroderma Complicated by Superimposed Bullous Majocchi\u2019s Granuloma: The Consequences of Skin Barrier Dysfunction"],"prefix":"10.3390","volume":"16","author":[{"given":"Tao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dermatology, Peking Union Medical College Hospital,  Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenchen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Peking Union Medical College Hospital,  Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Peking Union Medical College Hospital,  Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunjia","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Physiology,  Institute of Basic Medical Sciences and School of Basic Medicine,  Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Physiology,  Institute of Basic Medical Sciences and School of Basic Medicine,  Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bill","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts, Worcester, MA 01655, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham & Women's Hospital, Harvard Medical School,  221 Longwood Ave. EBRC 401, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham & Women's Hospital, Harvard Medical School,  221 Longwood Ave. EBRC 401, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuehua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Peking Union Medical College Hospital,  Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham & Women's Hospital, Harvard Medical School,  221 Longwood Ave. EBRC 401, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1046\/j.1365-2230.2003.01295.x","article-title":"The clinical spectrum of nonbullous congenital ichthyosiform erythroderma and lamellar ichthyosis","volume":"28","author":"Akiyama","year":"2003","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1001\/archderm.1985.01660040061013","article-title":"Heterogeneity in autosomal recessive ichthyosis. Clinical and biochemical differentiation of lamellar ichthyosis and nonbullous congenital ichthyosiform erythroderma","volume":"121","author":"Williams","year":"1985","journal-title":"Arch. Dermatol."},{"key":"ref_3","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 soreze 2009","volume":"63","author":"Oji","year":"2010","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_4","unstructured":"Bolognia, J.L., Jorizzo, J.L., and Schaffer, J.V. (2012). Dermatology, Dermatology."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1194\/jlr.R800002-JLR200","article-title":"Pathogenesis of permeability barrier abnormalities in the ichthyoses: Inherited disorders of lipid metabolism","volume":"49","author":"Elias","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"49S","DOI":"10.1111\/1523-1747.ep12388591","article-title":"The genetics of ichthyosis: A primer for epidemiologists","volume":"102","author":"Bale","year":"1994","journal-title":"J. Investig. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1093\/hmg\/ddl249","article-title":"Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: Evidence for a temperature-sensitive phenotype","volume":"15","author":"Oji","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e29500","DOI":"10.1371\/journal.pone.0029500","article-title":"Identification of sequence variants in genetic disease-causing genes using targeted next-generation sequencing","volume":"6","author":"Wei","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/jid.2009.346","article-title":"Genotypic and clinical spectrum of self-improving collodion ichthyosis: ALOX12B, ALOXE3, and TGM1 mutations in Scandinavian patients","volume":"130","author":"Vahlquist","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1038\/jid.2008.409","article-title":"Molecular analysis of 250 patients with autosomal recessive congenital ichthyosis: Evidence for mutation hotspots in ALOXE3 and allelic heterogeneity in ALOX12B","volume":"129","author":"Eckl","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/humu.20236","article-title":"Mutation spectrum and functional analysis of epidermis-type lipoxygenases in patients with autosomal recessive congenital ichthyosis","volume":"26","author":"Eckl","year":"2005","journal-title":"Hum. Mutat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1093\/hmg\/11.1.107","article-title":"Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1","volume":"11","author":"Jobard","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1038\/jid.2012.160","article-title":"The expression of epidermal lipoxygenases and transglutaminase-1 is perturbed by NIPAL4 mutations: Indications of a common metabolic pathway essential for skin barrier homeostasis","volume":"132","author":"Li","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_14","first-page":"270","article-title":"Autosomal recessive congenital ichthyosis","volume":"104","author":"Bale","year":"2013","journal-title":"Actas Dermosifiliogr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/jid.2012.250","article-title":"Aloxe3 knockout mice reveal a function of epidermal lipoxygenase-3 as hepoxilin synthase and its pivotal role in barrier formation","volume":"133","author":"Krieg","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.bbalip.2013.08.005","article-title":"The role of lipoxygenases in epidermis","volume":"1841","author":"Krieg","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.bbalip.2013.08.011","article-title":"Ceramide synthesis in the epidermis","volume":"1841","author":"Rabionet","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9162","DOI":"10.1073\/pnas.1633612100","article-title":"The lipoxygenase gene ALOXE3 implicated in skin differentiation encodes a hydroperoxide isomerase","volume":"100","author":"Yu","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1038\/jid.2009.57","article-title":"Autosomal recessive congenital ichthyosis","volume":"129","author":"Fischer","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/sj.jid.5700640","article-title":"Novel mutations in ALOX12B in patients with autosomal recessive congenital ichthyosis and evidence for genetic heterogeneity on chromosome 17p13","volume":"127","author":"Lesueur","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1101\/gr.088013.108","article-title":"SNP detection for massively parallel whole-genome resequencing","volume":"19","author":"Li","year":"2009","journal-title":"Genome Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/9\/21791\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:48:12Z","timestamp":1760215692000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/9\/21791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,9]]},"references-count":21,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2015,9]]}},"alternative-id":["ijms160921791"],"URL":"https:\/\/doi.org\/10.3390\/ijms160921791","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2015,9,9]]}}}