{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T05:19:46Z","timestamp":1788067186335,"version":"build-2784847793"},"reference-count":89,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T00:00:00Z","timestamp":1672617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004681","name":"Higher Education Commission","doi-asserted-by":"publisher","award":["5265\/NRPU\/HEC\/2016"],"award-info":[{"award-number":["5265\/NRPU\/HEC\/2016"]}],"id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alexandervon-Humboldt Foundation","award":["5265\/NRPU\/HEC\/2016"],"award-info":[{"award-number":["5265\/NRPU\/HEC\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Lamellar ichthyosis is a rare skin disease characterized by large, dark brown plate-like scales on the entire body surface with minimum or no erythema. This phenotype is frequently associated with a mutation in the TGM1 gene, encoding the enzyme transglutaminase 1 which plays a catalytic role in the formation of the cornified cell envelop. The present study aimed to carry out clinical and genetic characterization of the autosomal recessive lamellar ichthyosis family from Balochistan. Materials and Methods: A consanguineous family with lamellar ichthyosis was enrolled from Balochistan, Pakistan. PCR amplification of all the exons and splice site junctions of the TGM1 gene followed by Sanger sequencing was performed on the genomic DNA. The identified variant was checked by In silico prediction tools to evaluate the effect of the variant on protein. Results: Sanger sequencing identified a homozygous nonsense variant c.131G &gt;A (p.Trp44*) in the TGM1 gene that segregated in the autosomal recessive mode of inheritance in the family. The identified variant results in premature termination of transcribed mRNA and is predicted to cause a truncated or absent translation product transglutaminase-1 (TGase-1) accompanied by loss of catalytic activity, causing a severe clinical phenotype of lamellar ichthyosis in the patients. Conclusions: Here, we report a consanguineous lamellar ichthyosis family with a homozygous nonsense variant in the TGM1 gene. The variant is predicted as pathogenic by different In silico prediction tools.<\/jats:p>","DOI":"10.3390\/medicina59010103","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T02:05:53Z","timestamp":1672711553000},"page":"103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification and In Silico Analysis of a Homozygous Nonsense Variant in TGM1 Gene Segregating with Congenital Ichthyosis in a Consanguineous Family"],"prefix":"10.3390","volume":"59","author":[{"given":"Abdulhadi","family":"Almazroea","sequence":"first","affiliation":[{"name":"Pediatrician, Associate Professor at College of Medicine, Taibah University, Madinah 41477, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7748-5323","authenticated-orcid":false,"given":"Ambreen","family":"Ijaz","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Life Sciences & Informatics, BUITEMS, Quetta 87300, Pakistan"},{"name":"Department of Zoology, SBK Women\u2019s University, Quetta 87500, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Aziz","sequence":"additional","affiliation":[{"name":"Department of Computer Sciences and Bioinformatics, Khushal Khan Khattak University, Karak 27200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0896-3720","authenticated-orcid":false,"given":"Muhammad","family":"Mushtaq Yasinzai","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Life Sciences & Informatics, BUITEMS, Quetta 87300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafiullah","family":"Rafiullah","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Life Sciences & Informatics, BUITEMS, Quetta 87300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fazal Ur","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Balochistan, Quetta 87550, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakeela","family":"Daud","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Life Sciences & Informatics, BUITEMS, Quetta 87300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rozeena","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Life Sciences & Informatics, BUITEMS, Quetta 87300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ayub","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, University of Balochistan, Quetta 87550, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Wali","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Life Sciences & Informatics, BUITEMS, Quetta 87300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Elias, P.M. (2010). Ichthyoses, Clinical, Biochemical, Pathogenic and Diagnostic Assessment, Karger Medical and Scientific Publishers.","DOI":"10.1159\/isbn.978-3-8055-9395-3"},{"key":"ref_2","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 Sor\u00e8ze 2009","volume":"63","author":"Oji","year":"2010","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_3","unstructured":"Yoneda, K.T.K., Iizuka, H., Shimizu, H., Tomita, Y.M.Y., and Hashimoto, K. (2003). Comprehensive Handbook of Clinical Dermatology, Nakayamashoten."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2165\/11311070-000000000-00000","article-title":"Ichthyosis: Clinical manifestations and practical treatment options","volume":"10","author":"Oji","year":"2009","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_5","first-page":"483","article-title":"Analysis of the VCX3A, VCX2 and VCX3B genes shows that VCX3A gene deletion is not sufficient to result in mental retardation in X-linked ichthyosis","volume":"158","year":"2008","journal-title":"Br. J. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/cge.12828","article-title":"A practical approach to ichthyoses with systemic manifestations","volume":"91","author":"Saral","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_7","unstructured":"Richard, G., Adam, M.P., Everman, D.B., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Amemiya, A. (1993). Autosomal Recessive Congenital IchthyosisIn: GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1111\/j.1365-2133.2009.09339.x","article-title":"Filaggrin haploinsufficiency is highly penetrant and is associated with increased severity of eczema: Further delineation of the skin phenotype in a prospective epidemiological study of 792 school children","volume":"161","author":"Brown","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"186","DOI":"10.2340\/00015555-3432","article-title":"Genetics of Inherited Ichthyoses and Related Diseases","volume":"100","author":"Fischer","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1365-2133.2010.09745.x","article-title":"Partially disturbed lamellar granule secretion in mild congenital ichthyosiform erythroderma with ALOX12B mutations","volume":"163","author":"Akiyama","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/ng2020","article-title":"Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema","volume":"39","author":"Sandilands","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_12","first-page":"644","article-title":"Molecular studies of ichthyosis vulgaris in Pakistani families","volume":"20","author":"Samdani","year":"2010","journal-title":"J. Coll. Physicians Surg. Pak."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"xxxvi","DOI":"10.1046\/j.0022-202X.2004.22233.x","article-title":"The Epidermal Permeability Barrier: From the Early Days at Harvard to Emerging Concepts","volume":"122","author":"Elias","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.jaad.2014.12.020","article-title":"The phenotype spectrum of X-linked ichthyosis identified by chromosomal microarray","volume":"72","author":"Hand","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jdermsci.2006.10.001","article-title":"Deletion of distal promoter of VCXA in a patient with X-linked ichthyosis associated with borderline mental retardation","volume":"45","author":"Hosomi","year":"2007","journal-title":"J. Dermatol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jsbmb.2006.12.105","article-title":"Immunohistochemical analysis of steroid sulfatase in human tissues","volume":"105","author":"Selcer","year":"2007","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1172\/JCI24834","article-title":"Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer","volume":"115","author":"Akiyama","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1089\/gtmb.2018.0310","article-title":"Molecular Genetic Study of a Large Inbred Pakistani Family Affected with Autosomal Recessive Congenital Ichthyosis Through Whole Exome Sequencing","volume":"23","author":"Karim","year":"2019","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"17702","DOI":"10.1074\/jbc.270.30.17702","article-title":"The Proteins Elafin, Filaggrin, Keratin Intermediate Filaments, Loricrin, and Small Proline-rich Proteins 1 and 2 Are Isodipeptide Cross-linked Components of the Human Epidermal Cornified Cell Envelope","volume":"270","author":"Steinert","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jdermsci.2006.01.003","article-title":"Harlequin ichthyosis and other autosomal recessive congenital ichthyoses: The underlying genetic defects and pathomechanisms","volume":"42","author":"Akiyama","year":"2006","journal-title":"J. Dermatol. Sci."},{"key":"ref_21","first-page":"270","article-title":"Autosomal recessive congenital ichthyosis","volume":"104","author":"Ginarte","year":"2013","journal-title":"Actas Dermosifiliogr."},{"key":"ref_22","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_23","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. Invest. Dermatol."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000265757","article-title":"NIPAL4\/ichthyin is expressed in the granular layer of human epidermis and mutated in two Pakistani families with autosomal recessive ichthyosis","volume":"220","author":"Wajid","year":"2010","journal-title":"J. Dermatol."},{"key":"ref_26","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Mefford, H.C., Stephens, K., Amemiya, A., and Ledbetter, N. (2001). Autosomal recessive congenital ichthyosis. GeneReviews, University of Washington. Last Update: Updated 2017 edn 23."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/ng0395-279","article-title":"Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis","volume":"9","author":"Russell","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/1346-8138.13243","article-title":"Inherited ichthyosis: Non-syndromic forms","volume":"43","author":"Takeichi","year":"2016","journal-title":"J. Dermatol."},{"key":"ref_29","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. Invest. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33540","DOI":"10.1074\/jbc.273.50.33540","article-title":"Human 12 (R)-lipoxygenase and the mouse ortholog molecular cloning, expression, and gene chromosomal assignment","volume":"273","author":"Sun","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s11745-000-0576-0","article-title":"Diversity of mouse lipoxygenases: Identification of a subfamily of epidermal isozymes exhibiting a differentiation-dependent mRNA expression pattern","volume":"35","author":"Heidt","year":"2000","journal-title":"Lipids"},{"key":"ref_32","first-page":"390","article-title":"The role of lipoxygenases in epidermis","volume":"1841","author":"Krieg","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_33","first-page":"169","article-title":"Identification and characterization of a novel ABCA subfamily member, ABCA12, located in the lamellar ichthyosis region on 2q34. Cytogenet","volume":"98","author":"Annilo","year":"2002","journal-title":"Genome Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/j.1600-0625.2007.00614.x","article-title":"Localization of ABCA12 from Golgi apparatus to lamellar granules in human upper epidermal keratinocytes","volume":"16","author":"Sakai","year":"2007","journal-title":"Exp. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1093\/hmg\/ddg235","article-title":"Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2","volume":"12","author":"Audebert","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1086\/429844","article-title":"Mutations in ABCA12 Underlie the Severe Congenital Skin Disease Harlequin Ichthyosis","volume":"76","author":"Kelsell","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1093\/hmg\/ddh263","article-title":"Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congnital ichthyosis","volume":"13","author":"Bouadjar","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1001\/archderm.144.3.351","article-title":"Self-healing collodion membrane and mild nonbullous congenital ichthyosiform erythroderma due to 2 novel mutations in the ALOX12B gene","volume":"144","author":"Harting","year":"2008","journal-title":"Arch. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1086\/302813","article-title":"Assignment of a Novel Locus for Autosomal Recessive Congenital Ichthyosis to Chromosome 19p13.1-p13.2","volume":"66","author":"Virolainen","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7707","DOI":"10.1073\/pnas.1503491112","article-title":"Essential role of the cytochrome P450 CYP4F22 in the production of acylceramide, the key lipid for skin permeability barrier formation","volume":"112","author":"Ohno","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1002\/humu.23594","article-title":"Mutation update for CYP4F22 variants associated with autosomal recessive congenital ichthyosis","volume":"39","author":"Hotz","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Radner, F.P., Marrakchi, S., Kirchmeier, P., Kim, G.J., Ribierre, F., Kamoun, B., Abid, L., Leipoldt, M., Turki, H., and Schempp, W. (2013). Mutations in CERS3 cause autosomal recessive congenital ichthyosis in humans. PLoS Genet., 9.","DOI":"10.1371\/annotation\/df5af830-8e1d-495a-a206-f881ed85e7fe"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1038\/jid.2013.153","article-title":"Impaired Epidermal Ceramide Synthesis Causes Autosomal Recessive Congenital Ichthyosis and Reveals the Importance of Ceramide Acyl Chain Length","volume":"133","author":"Eckl","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/ng.1056","article-title":"PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans","volume":"44","author":"Grall","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jid.2016.08.036","article-title":"PNPLA1 Deficiency in Mice and Humans Leads to a Defect in the Synthesis of Omega-O-Acylceramides","volume":"137","author":"Grond","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14609","DOI":"10.1038\/ncomms14609","article-title":"PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis","volume":"8","author":"Hirabayashi","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"14610","DOI":"10.1038\/ncomms14610","article-title":"PNPLA1 is a transacylase essential for the generation of the skin barrier lipid \u03c9-O-acylceramide","volume":"8","author":"Ohno","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e210","DOI":"10.1111\/jdv.13540","article-title":"A novel missense variant in the PNPLA1 gene underlies congenital ichthyosis in three consanguineous families","volume":"30","author":"Ahmad","year":"2016","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1111\/bjd.12757","article-title":"Identification of a novel PNPLA1 mutation in a Spanish family with autosomal recessive congenital ichthyosis","volume":"170","author":"Fachal","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"932","DOI":"10.2340\/00015555-2418","article-title":"Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia: Clinical Characteristics and Novel and Recurrent Mutations in 132 Patients","volume":"96","author":"Pigg","year":"2016","journal-title":"Acta Derm. Venereol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.jid.2016.11.012","article-title":"Gene-Targeted Next Generation Sequencing Identifies PNPLA1 Mutations in Patients with a Phenotypic Spectrum of Autosomal Recessive Congenital Ichthyosis: The Impact of Consanguinity","volume":"137","author":"Vahidnezhad","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_52","first-page":"357","article-title":"Analysis of clinical phenotype and TGM1 gene mutation in a child with neonatal congenital ichthyosis","volume":"36","author":"Hu","year":"2019","journal-title":"Cmaj"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: A program to check the stereochemical quality of protein structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J. Appl. Crystallogr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/bmb.20966","article-title":"Using the PyMOL application to reinforce visual understanding of protein structure","volume":"44","author":"Rigsby","year":"2016","journal-title":"Biochem. Mol. Biol. Educ."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1136\/jmg.2008.060905","article-title":"Novel transglutaminase-1 mutations and genotype-phenotype investigations of 104 patients with autosomal recessive congenital ichthyosis in the USA","volume":"46","author":"Farasat","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1111\/j.1365-4632.2009.04223.x","article-title":"Lamellar ichthyosis with a novel homozygous C-terminal mutation in the transglutaminase-1 gene","volume":"48","author":"Ginarte","year":"2009","journal-title":"Int. J. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1159\/000248031","article-title":"Cornified Cell Envelope","volume":"180","author":"Hohl","year":"1990","journal-title":"Dermatology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1096\/fasebj.5.15.1683845","article-title":"Transglutaminases: Multifunctional cross linking enzymes that stabilize tissues","volume":"5","author":"Greenberg","year":"1991","journal-title":"FASEB J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1034\/j.1600-0625.2001.110308.x","article-title":"Basis for the permeability barrier abnormality in lamellar ichthyosis","volume":"11","author":"Elias","year":"2002","journal-title":"Exp. Dermatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1126\/science.7824952","article-title":"Mutations of Keratinocyte Transglutaminase in Lamellar Ichthyosis","volume":"267","author":"Huber","year":"1995","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0625.1998.tb00295.x","article-title":"Structural organization of cornified cell envelopes and alterations in inherited skin disorders","volume":"7","author":"Iizuka","year":"1998","journal-title":"Exp. Dermatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.jaad.2011.07.033","article-title":"Prevalence of autosomal recessive congenital ichthyosis: A population-based study using the capture-recapture method in Spain","volume":"67","author":"Aranegui","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e416","DOI":"10.1038\/cddis.2012.152","article-title":"Novel transglutaminase 1 mutations in patients affected by lamellar ichthyosis","volume":"3","author":"Terrinoni","year":"2012","journal-title":"Cell Death Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"126","DOI":"10.4274\/MMJ.galenos.2022.39924","article-title":"Genetic Etiology of Ichthyosis in Turkish Patients: Next-generation Sequencing Identified Seven Novel Mutations","volume":"37","author":"Saat","year":"2022","journal-title":"Medeni. Med. J."},{"key":"ref_65","first-page":"583","article-title":"Compound Heterozygous Mutations in TGM1 Causing a Severe Form of Lamellar Ichthyosis: A Case Report","volume":"15","author":"Zeng","year":"2022","journal-title":"Pharm. Pers. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/pde.14128","article-title":"A case of self-improving collodion ichthyosis in Vietnam","volume":"37","author":"Diep","year":"2020","journal-title":"Pediatr. Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1001\/archdermatol.2011.9","article-title":"Harlequin ichthyosis: A review of clinical and molecular findings in 45 cases","volume":"147","author":"Rajpopat","year":"2011","journal-title":"Arch. Dermatol. Res."},{"key":"ref_68","first-page":"365","article-title":"Primer3 on the WWW for general users and for biologist programmers","volume":"132","author":"Rozen","year":"2000","journal-title":"Methods Mol. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nmeth.3213","article-title":"The I-TASSER Suite: Protein structure and function prediction","volume":"12","author":"Yang","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/prot.22570","article-title":"Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: Four approaches that performed well in CASP8","volume":"77","author":"Krieger","year":"2009","journal-title":"Proteins"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1126\/science.1853201","article-title":"A Method to Identify Protein Sequences That Fold into a Known Three-Dimensional Structure","volume":"253","author":"Bowie","year":"1991","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/pro.5560020916","article-title":"Verification of protein structures: Patterns of nonbonded atomic interactions","volume":"2","author":"Colovos","year":"1993","journal-title":"Protein Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/381272a0","article-title":"Errors in protein structures","volume":"381","author":"Hooft","year":"1996","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1080\/00015550310002666","article-title":"Autosomal recessive congenital ichthyosis in Sweden and Estonia: Clinical, genetic and ultrastructural findings in eighty-three patients","volume":"83","author":"Ganemo","year":"2003","journal-title":"Acta. Derm.Venereol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1159\/000349914","article-title":"Transglutaminase-1 Mutations in Omani Families with Lamellar Ichthyosis","volume":"22","year":"2013","journal-title":"Med. Princ. Pr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1001\/archdermatol.2012.1947","article-title":"Specific TGM1 mutation profiles in bathing suit and self improving collodion ichthyoses: Phenotypic and genotypic data from 9 patients with dynamic phenotypes of autosomal recessive congenital ichthyosis","volume":"148","author":"Bourrat","year":"2012","journal-title":"Arch. Dermatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/j.1365-2133.2011.10454.x","article-title":"Analysis of TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 in autosomal recessive congenital ichthyosis from Galicia (NW Spain): Evidence of founder effects","volume":"165","author":"Ginarte","year":"2011","journal-title":"Br. J. Dermatol."},{"key":"ref_78","first-page":"e14152","article-title":"Mild lamellar ichthyosis with a truncated homozygousTGM1mutation in a pediatric patient from Turkey","volume":"33","author":"Tanacan","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/humu.23695","article-title":"Autosomal recessive congenital ichthyosis: Genomic landscape and phenotypic spectrum in a cohort of 125 consanguineous families","volume":"40","author":"Youssefian","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/humu.20952","article-title":"Transglutaminase-1 gene mutations in autosomal recessive congenital ichthyosis: Summary of mutations (including 23 novel) and modeling of TGase-1","volume":"30","author":"Herman","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.prostaglandins.2006.05.006","article-title":"Role of epidermis-type lipoxygenases for skin barrier function and adipocyte differentiation","volume":"82","author":"Epp","year":"2007","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1093\/hmg\/4.8.1391","article-title":"Autosomal recessive lamellar ichthyosis: Identification of a new mutation in transglutaminase 1 and evidence for genetic heterogeneity","volume":"4","author":"Parmentier","year":"1995","journal-title":"Hum. Mol. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"13693","DOI":"10.1074\/jbc.273.22.13693","article-title":"Transglutaminase 1 mutations in lamellar ichthyosis Loss of activity due to failure of activation by proteolytic processing","volume":"273","author":"Candi","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1111\/ijd.12950","article-title":"Novel mutations in the genes TGM 1 and ALOXE 3 underlying autosomal recessive congenital ichthyosis","volume":"55","author":"Ullah","year":"2016","journal-title":"Int. J. Dermatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.pedneo.2018.01.003","article-title":"Novel TGM1 mutation in a Pakistani family affected with severe lamellar ichthyosis","volume":"59","author":"Rasheed","year":"2018","journal-title":"Pediatr. Neonatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"26382","DOI":"10.1074\/jbc.270.44.26382","article-title":"Biochemical, Structural, and Transglutaminase Substrate Properties Of Human Loricrin, the Major Epidermal Cornified Cell Envelope Protein","volume":"270","author":"Candi","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"26382","DOI":"10.1074\/jbc.270.44.26382","article-title":"Transglutaminase Cross-linking Properties of the Small Proline-rich 1 Family of Cornified Cell Envelope Proteins","volume":"270","author":"Candi","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/bjd.17203","article-title":"Management of congenital ichthyoses: European guidelines of care, part one","volume":"180","author":"Vahlquist","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/bjd.16882","article-title":"Management of congenital ichthyoses: European guidelines of care, part two","volume":"180","author":"Bygum","year":"2019","journal-title":"Br. J. Dermatol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/1\/103\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:56:38Z","timestamp":1760118998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/1\/103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,2]]},"references-count":89,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["medicina59010103"],"URL":"https:\/\/doi.org\/10.3390\/medicina59010103","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,2]]}}}