{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:26:39Z","timestamp":1780669599125,"version":"3.54.1"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education and Scientific Research, Tunisia"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The <jats:italic>NIPAL4<\/jats:italic> gene is described to be implicated of Congenital Ichthyosiform Erythroderma (CIE). It encodes a magnesium transporter membrane\u2010associated protein, hypothetically involved in epidermal lipid processing and in lamellar body formation. The aim of this work is to investigate the causative mutation in a consanguineous Tunisian family with a clinical feature of CIE with a yellowish severe palmoplantar keratoderma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four patients were dignosed with CIE. The blood samples were collected from patients and all members of their nuclear family for mutation analysis. The novel mutation of NIPAL4 gene was analysed with several software tools to predict its pathogenicity. Then, the secondary structure and the 3D model of ichthyn was generated in silico.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The sequencing analysis of the <jats:italic>NIPAL4<\/jats:italic> gene in patients revealed a novel homozygous missense mutation c.534A&gt;C (p.E178D) in the exon 4. Bioinformatic tools predicted its pathogenicity. The secondary structure prediction and the 3D model construction expected the presence of 9 transmembrane helices and revealed that mutation p.E178D was located in the middle of the second transmembrane helices. Besides, the 3D model construction revealed that the p.E178D mutation is inducing a shrinking in the transport channel containing the mutated NIPA4 protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We found a homozygous mutation in exon 4 of NIPAL4 c.534A&gt;C (p.E178D), which was identified for the first time in our study. Bioinformatic investigations supported its involvement in the phenotype of patients with CIE. Interestingly, this mutation was located in the hypothetical transport channel cavity and leads to changes in the channel architecture, which would probably affect its transport function.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1104","type":"journal-article","created":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T09:45:11Z","timestamp":1577353511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of a novel missense mutation in <i>NIPAL4 <\/i>gene: First 3D model construction predicted its pathogenicity"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7893-9232","authenticated-orcid":false,"given":"Sahar","family":"Laadhar","sequence":"first","affiliation":[{"name":"Faculty of Sciencs of Sfax Laboratory of Molecular and Functional Genetics Sfax Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riadh","family":"Ben Mansour","sequence":"additional","affiliation":[{"name":"Laboratory of Food Analysis Valorization and Security, Research Group \"Biotechnology and pathologies\" National School of Engineer of Sfax Sfax Tunisia"},{"name":"Faculty of Sciences of Gafsa Department of Life Sciences Gafsa Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slaheddine","family":"Marrakchi","sequence":"additional","affiliation":[{"name":"Dermatology Department HediChaker Hospital Sfax Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil","family":"Miled","sequence":"additional","affiliation":[{"name":"Faculty of Sciences Department of Biological Sciences University of Jeddah Jeddah KSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariem","family":"Ennouri","sequence":"additional","affiliation":[{"name":"Faculty of Sciencs of Sfax Laboratory of Molecular and Functional Genetics Sfax Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Medical Center\u2010University of Freiburg Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Ali","family":"Kaddechi","sequence":"additional","affiliation":[{"name":"Regional Health Administration of Sidi Bouzid Sidi Bouzid Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamida","family":"Turki","sequence":"additional","affiliation":[{"name":"Dermatology Department HediChaker Hospital Sfax Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiza","family":"Fakhfakh","sequence":"additional","affiliation":[{"name":"Faculty of Sciencs of Sfax Laboratory of Molecular and Functional Genetics Sfax Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,26]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2230.2003.01295.x"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2011.01412.x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx369"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv195"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6MD00005C"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.050542"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-012-1207-7"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.57"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/302814"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610314200"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00091.2008"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-2550"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh263"},{"key":"e_1_2_12_15_1","first-page":"522","article-title":"A simple method for DNA extraction from leukocytes for use in PCR","volume":"13","author":"Lewin H. 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