{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:26:21Z","timestamp":1790753181280,"version":"4.1.0"},"reference-count":16,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,26]],"date-time":"2024-05-26T00:00:00Z","timestamp":1716681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"General Sub-Direction of Evaluation and Research Promotion of the Carlos III Institute of Health and co-funded with FEDER funds","award":["PI17\/0796"],"award-info":[{"award-number":["PI17\/0796"]}]},{"name":"General Sub-Direction of Evaluation and Research Promotion of the Carlos III Institute of Health and co-funded with FEDER funds","award":["PI21\/1082"],"award-info":[{"award-number":["PI21\/1082"]}]},{"name":"Ectodermal Dysplasia Patients in Spain","award":["PI17\/0796"],"award-info":[{"award-number":["PI17\/0796"]}]},{"name":"Ectodermal Dysplasia Patients in Spain","award":["PI21\/1082"],"award-info":[{"award-number":["PI21\/1082"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>HELIX syndrome (Hypohidrosis\u2013Electrolyte disturbances\u2013hypoLacrimia\u2013Ichthyosis\u2013Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 \u00d7 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling.<\/jats:p>","DOI":"10.3390\/genes15060687","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T10:14:07Z","timestamp":1716804847000},"page":"687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["HELIX Syndrome, a Claudinopathy with Relevant Dermatological Manifestations: Report of Two New Cases"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1853-3203","authenticated-orcid":false,"given":"Mar\u00eda Carmen","family":"Mart\u00ednez-Romero","sequence":"first","affiliation":[{"name":"Molecular Genetics Section, Biochemistry and Clinical Genetics Center, University Clinical Hospital Virgen de la Arrixaca, 30120 Murcia, Spain"},{"name":"Pediatric Research, Murcian Institute for Biosanitary Research (IMIB) Pascual Parrilla, 30120 Murcia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Carlos III Health Institute, 28029 Madrid, Spain"},{"name":"Faculty of Medicine, UCAM Catholic University of Murcia, 30109 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Encarnaci\u00f3n","family":"Hern\u00e1ndez-Contreras","sequence":"additional","affiliation":[{"name":"Internal Medicine Service, University Clinical Hospital Virgen de la Arrixaca, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio","family":"Bafalliu-Vidal","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Biochemistry and Clinical Genetics Center, University Clinical Hospital Virgen de la Arrixaca, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4728-8174","authenticated-orcid":false,"given":"Mar\u00eda","family":"Barreda-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Pediatric Research, Murcian Institute for Biosanitary Research (IMIB) Pascual Parrilla, 30120 Murcia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Carlos III Health Institute, 28029 Madrid, Spain"},{"name":"Faculty of Medicine, UCAM Catholic University of Murcia, 30109 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Mart\u00ednez-Mench\u00f3n","sequence":"additional","affiliation":[{"name":"Dermatology Department, University Clinical Hospital Virgen de la Arrixaca, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Cabello-Chaves","sequence":"additional","affiliation":[{"name":"Nephrology Department, University Clinical Hospital Virgen del Roc\u00edo, 41013 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2915-7381","authenticated-orcid":false,"given":"Encarna","family":"Guill\u00e9n-Navarro","sequence":"additional","affiliation":[{"name":"Pediatric Research, Murcian Institute for Biosanitary Research (IMIB) Pascual Parrilla, 30120 Murcia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Carlos III Health Institute, 28029 Madrid, Spain"},{"name":"Pediatrics Department, University Clinical Hospital Virgen de la Arrixaca, 30120 Murcia, Spain"},{"name":"Surgery, Pediatrics, Obstetrics and Gynecology Department, University of Murcia (UMU), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/gim.2017.71","article-title":"Multiplex epithelium dysfunction due to CLDN10 mutation: The HELIX syndrome","volume":"20","author":"Brideau","year":"2018","journal-title":"Genet. 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Mutat."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/6\/687\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:48:54Z","timestamp":1760107734000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/6\/687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,26]]},"references-count":16,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["genes15060687"],"URL":"https:\/\/doi.org\/10.3390\/genes15060687","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,26]]}}}