{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:59:21Z","timestamp":1790402361720,"version":"4.1.0"},"reference-count":16,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"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>Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) is a fatty acid elongase responsible for very long-chain fatty acid biosynthesis in the brain, retina, and skin. Heterozygous mutations in ELOVL4 gene cause Stargardt-like macular dystrophy and spinocerebellar ataxia type-34, while different homozygous mutations have been associated with ichthyosis, spastic quadriplegia, and mental retardation syndrome in three kindred. We report the first two Italian children affected with neuro-ichthyosis due to the previously undescribed ELOVL4 homozygous frameshift variant c.435dupT (p.Ile146TyrfsTer29), and compound heterozygous variants c.208C&gt;T (p.Arg70Ter) and c.487T&gt;C (p.Cys163Arg), respectively. Both patients were born with collodion membrane followed by development of diffuse mild hyperkeratosis and scaling, localized erythema, and palmoplantar keratoderma. One infant displayed mild facial dysmorphism. They suffered from failure to thrive, and severe gastro-esophageal reflux with pulmonary aspiration. The patients presented axial hypotonia, hypertonia of limbs, and absent head control with poor eye contact from infancy. Visual evoked potentials showed markedly increased latency and poor morphological definition, indicative of alteration of the retro-retinal visual pathways in both patients. Ultrastructural skin examination revealed abnormalities of lamellar bodies with altered release in the epidermal granular and horny layer intracellular spaces. Our findings contribute to expanding the phenotypic and genotypic features of ELOVL4-related neuro-ichthyosis.<\/jats:p>","DOI":"10.3390\/genes12030343","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T06:47:20Z","timestamp":1614322040000},"page":"343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Two Italian Patients with ELOVL4-Related Neuro-Ichthyosis: \u00a0Expanding the Genotypic and Phenotypic Spectrum and Ultrastructural Characterization"],"prefix":"10.3390","volume":"12","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 Sant\u2019Onofrio 4, 00165 Rome, Italy"},{"name":"Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5612-821X","authenticated-orcid":false,"given":"Francesco","family":"Nicita","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cesario","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Pisaneschi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Macchiaiolo","sequence":"additional","affiliation":[{"name":"Rare Diseases and Medical Genetics Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Rossi","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio, 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":"Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Zambruno","sequence":"additional","affiliation":[{"name":"Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 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 Sant\u2019Onofrio 4, 00165 Rome, Italy"},{"name":"Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.3389\/fncel.2019.00428","article-title":"Novel Cellular Functions of Very Long Chain-Fatty Acids: Insight from ELOVL4 Mutations","volume":"13","author":"Anderson","year":"2019","journal-title":"Front. 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