{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:12:11Z","timestamp":1784772731299,"version":"3.55.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Epidermolysis bullosa (EB) is a genetic skin disorder that shows heterogeneous clinical fragility. The patients develop skin blisters congenitally or in the early years of life at the dermo-epithelial junctions, including erosions, hyperkeratosis over the palms and soles. The other associated features are hypotrichosis on the scalp, absent or dystrophic nails, and dental anomalies. Molecular diagnosis through whole-exome sequencing (WES) has become one of the successful tool in clinical setups. In this study, three Pakhtun families from the Khyber Pakhtunkhwa province of Pakistan were ascertained. WES analysis of a proband in each family revealed two novel variants (COL17A1: NM_000494.4: c.4041T&amp;gt;G: p.Y1347<jats:sup>*<\/jats:sup> and PLEC: NM_201380.3: c.1283_1285delGCT: p.L426del) and one previously known COL17A1: NM_000494.4:c.3067C&amp;gt;T: p.Q1023<jats:sup>*<\/jats:sup>) variant in homozygous forms. Sanger sequencing of the identified variants confirmed that the heterozygous genotypes of the obligate carriers. The identified variants have not only increased the mutation spectrum of the COL17A1 and PLEC but also confirms their vital role in the morphogenesis of skin and its associated appendages. WES can be used as a first-line diagnostic tool in genetic testing and counselling families from Khyber Pakhtunkhwa, Pakistan.<\/jats:p>","DOI":"10.3389\/fped.2021.727288","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T06:09:12Z","timestamp":1627970952000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Whole Exome Sequencing Confirms Molecular Diagnostics of Three Pakhtun Families With Autosomal Recessive Epidermolysis Bullosa"],"prefix":"10.3389","volume":"9","author":[{"given":"Fozia","family":"Fozia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubina","family":"Nazli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nousheen","family":"Bibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sher Alam","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor","family":"Muhammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nafila","family":"Shakeeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saadullah","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musharraf","family":"Jelani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveed","family":"Wasif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1001\/jamadermatol.2016.2473","article-title":"Epidemiology of inherited epidermolysis bullosa based on incidence and prevalence estimates from the national epidermolysis bullosa registry","volume":"152","author":"Fine","year":"2016","journal-title":"JAMA Dermatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1111\/bjd.18921","article-title":"Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility","volume":"183","author":"Has","year":"2020","journal-title":"Br J Dermatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1111\/jdv.17060","article-title":"Immunofluorescence mapping, electron microscopy and genetics in the diagnosis and sub-classification of inherited epidermolysis bullosa: a single-center retrospective comparative study of 87 cases with long-term follow-up","volume":"35","author":"Rossi","year":"2021","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1159\/000478856","article-title":"Diagnosis of inherited epidermolysis bullosa in resource-limited settings: immunohistochemistry revisited","volume":"233","author":"Yenamandra","year":"2017","journal-title":"Dermatology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0945-053X(98)00005-5","article-title":"Mutation analysis and molecular genetics of epidermolysis bullosa","volume":"18","author":"Pulkkinen","year":"1999","journal-title":"Matrix Biol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1111\/bjd.13190","article-title":"Whole-exome sequencing improves mutation detection in a diagnostic epidermolysis bullosa laboratory","volume":"172","author":"Takeichi","year":"2015","journal-title":"Br J Dermatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/s41572-020-0210-0","article-title":"Epidermolysis bullosa","volume":"6","author":"Bardhan","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"B8","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1111\/ahg.12123","article-title":"Identification of two homozygous sequence variants in the COL7A1 gene underlying dystrophic epidermolysis bullosa by whole-exome analysis in a consanguineous family","volume":"79","author":"Serafi","year":"2015","journal-title":"Ann Hum Genet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1471-2105-9-40","article-title":"I-TASSER server for protein 3D structure prediction","volume":"9","author":"Zhang","year":"2008"},{"key":"B10","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1107\/S0907444909042073","article-title":"MolProbity: all-atom structure validation for macromolecular crystallography. 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