{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T20:42:53Z","timestamp":1780605773608,"version":"3.54.1"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"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>Background: Ichthyoses are a large group of hereditary cornification disorders, which are both clinically and etiologically heterogeneous and affect mostly all the skin surface of the patients. Ichthyosis has its origin in an ancient Greek word \u201cichthys\u201d meaning fish, this is because the ichthyosis patients have dry, thickened, and scaly skin. There is an excess accumulation of epidermal cells resulting in the appearance of continuous and widespread scales on the body. There are many varieties of ichthyosis with a broad spectrum of intensity, severity, and associated symptoms, most of them are extremely rare. Ichthyosis vulgaris is the most frequently occurring type of ichthyoses. Method: The present study consists of four Pakistani ichthyosis families (A, B, C, and D). Whole exome sequencing (WES) approach was used to identify the pathogenic sequence variants in probands. The segregation of these variants in other participants was confirmed by Sanger sequencing. Results: Total four variants including, two splice site (TGM1: c.2088 + 1G &gt; A) and (SPINK5: c.882 + 1G &gt; T), a missense (SULT2B1: c.419C &gt; T; p. Ala140Val), and a nonsense (FLG: c.6109C &gt; T; p. Arg2037Ter) variant were identified in families A, C, B, and D, respectively, as causative mutations responsible for ichthyosis in these families. Conclusion: Our study unravels the molecular etiology of the four Pakistani ichthyosis families and validates the involvement of TGM1, SULT2B1, SPINK5, and FLG, in the etiology of different forms of ichthyosis. In addition, this study also aims to give a detailed clinical report of the studied ichthyosis families.<\/jats:p>","DOI":"10.3390\/genes12030373","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T11:46:09Z","timestamp":1614944769000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Novel Homozygous Mutations in the Genes TGM1, SULT2B1, SPINK5 and FLG in Four Families Underlying Congenital Ichthyosis"],"prefix":"10.3390","volume":"12","author":[{"given":"Fozia","family":"Fozia","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences (IBMS), Khyber Medical University (KMU), Peshawar 25100, Khyber Pakhtunkhwa, Pakistan"},{"name":"Department of Biotechnology and Genetic Engineering, Kohat University of Science &amp; Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubina","family":"Nazli","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences (IBMS), Khyber Medical University (KMU), Peshawar 25100, Khyber Pakhtunkhwa, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sher","family":"Alam Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering, Kohat University of Science &amp; Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-2361","authenticated-orcid":false,"given":"Ahmed","family":"Bari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2339-3500","authenticated-orcid":false,"given":"Abdul","family":"Nasir","sequence":"additional","affiliation":[{"name":"Department of Molecular Science and Technology, Ajou University, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2860-467X","authenticated-orcid":false,"given":"Riaz","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy (MAPPRC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hafiz Majid","family":"Mahmood","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8316-2336","authenticated-orcid":false,"given":"Muhammad","family":"Sohaib","sequence":"additional","affiliation":[{"name":"Department of Soil Sciences, College of Food and agriculture Sciences, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Alobaid","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3966-2282","authenticated-orcid":false,"given":"Siddique A.","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-6825","authenticated-orcid":false,"given":"Sulman","family":"Basit","sequence":"additional","affiliation":[{"name":"Center for Genetics and Inherited Diseases, Taibah University, Al-Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saadullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering, Kohat University of Science &amp; Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan"},{"name":"Center for Genetics and Inherited Diseases, Taibah University, Al-Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s40257-017-0313-x","article-title":"Inherited Nonsyndromic Ichthyoses: An Update on Pathophysiology, Diagnosis and Treatment","volume":"19","author":"Vahlquist","year":"2018","journal-title":"Am. 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