{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:42:51Z","timestamp":1785768171098,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR077563"],"award-info":[{"award-number":["R01AR077563"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Epidermolysis bullosa (EB) includes a group of rare gesnodermatoses that result in blistering and erosions of the skin and mucous membranes. Genetically, pathogenic variants in around 20 genes are known to alter the structural and functional integrity of intraepidermal adhesion and dermo-epidermal anchorage, leading to four different types of EB. Here we report the underlying genetic causes of EB phenotypes segregating in seven large consanguineous families, recruited from different regions of Pakistan. Whole exome sequencing, followed by segregation analysis of candidate variants through Sanger sequencing, identified eight pathogenic variants, including three novel (ITGB4: c.1285G&gt;T, and c.3373G&gt;A; PLEC: c.1828A&gt;G) and five previously reported variants (COL7A1: c.6209G&gt;A, and c.1573C&gt;T; FERMT1: c.676insC; LAMA3: c.151insG; LAMB3: c.1705C&gt;T). All identified variants were either absent or had very low frequencies in the control databases. Our in-silico analyses and 3-dimensional (3D) molecular modeling support the deleterious impact of these variants on the encoded proteins. Intriguingly, we report the first case of a recessively inherited form of rare EBS-Ogna associated with a homozygous variant in the PLEC gene. Our study highlights the clinical and genetic diversity of EB in the Pakistani population and expands the mutation spectrum of EB; it could also be useful for prenatal diagnosis and genetic counseling of the affected families.<\/jats:p>","DOI":"10.3390\/biom11050620","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T04:20:17Z","timestamp":1619065217000},"page":"620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Identification and Computational Analysis of Novel Pathogenic Variants in Pakistani Families with Diverse Epidermolysis Bullosa Phenotypes"],"prefix":"10.3390","volume":"11","author":[{"given":"Fehmida F.","family":"Khan","sequence":"first","affiliation":[{"name":"Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naima","family":"Khan","sequence":"additional","affiliation":[{"name":"Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2253-0750","authenticated-orcid":false,"given":"Sakina","family":"Rehman","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics and Translational Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Ejaz","sequence":"additional","affiliation":[{"name":"Army Medical College, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uzma","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Capital Hospital, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Erfan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Federal Government Polyclinic Hospital, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2914-4502","authenticated-orcid":false,"given":"Zubair M.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics and Translational Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3894-3085","authenticated-orcid":false,"given":"Muhammad","family":"Naeem","sequence":"additional","affiliation":[{"name":"Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.jaad.2008.02.004","article-title":"The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB","volume":"58","author":"Fine","year":"2008","journal-title":"J. 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