{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:43:05Z","timestamp":1761514985135,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"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: Inherited isolated nail clubbing is a very rare Mendelian condition in humans, characterized by enlargement of the terminal segments of fingers and toes with thickened nails. Mutations in two genes have been reported to cause isolated nail clubbing in humans, which are the SLCO2A1 gene and the HPGD gene. Objectives: An extended Pakistani family having two affected siblings born of unaffected consanguineous union was included in the study. Predominant isolated congenital nail clubbing (ICNC) without any other systemic abnormalities was observed, which we aimed to characterize at clinico-genetic level. Methods: Whole exome coupled with Sanger sequencing were employed to uncover the sequence variant as a cause of the disease. Furthermore, protein modeling was carried out to reveal the predicted possible effect of the mutation at the protein level. Results: Whole exome sequencing data analysis revealed a novel biallelic sequence variant (c.155T&gt;A; p.Phe52Tyr) in the SLCO2A1 gene. Further, Sanger sequencing analysis validated and confirmed the segregation of the novel variant in the entire family. Subsequently, protein modeling of the wild-type and mutated SLCO2A1 revealed broad-scale change, which might compromise the proteins\u2019 secondary structure and function. Conclusion: The present study adds another mutation to the SLCO2A1-related pathophysiology. The involvement of SLCO2A1 in the pathogenesis of ICNC may open exciting perceptions of this gene in nail development\/morphogenesis.<\/jats:p>","DOI":"10.3390\/genes14020430","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T02:32:07Z","timestamp":1675909927000},"page":"430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Homozygous Missense Variant in the Solute Carrier Organic Anion Transporter 2A1 (SLCO2A1) Gene Underlies Isolated Nail Clubbing"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6729-9746","authenticated-orcid":false,"given":"Muhammad","family":"Umair","sequence":"first","affiliation":[{"name":"Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNGH), King Saud Bin Abdulaziz University for Health Sciences, Riyadh 14611, Saudi Arabia"},{"name":"Department of Life Sciences, School of Science, University of Management and Technology (UMT), Lahore 54770, Punjab, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Bilal","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khadim","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale School of Medicine, Yale University, New Heaven, CT 06511, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulab","family":"Said","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Women University Swabi, Swabi 23430, Khyber Pakhtunkhwa (KPK), Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farooq","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Women University Swabi, Swabi 23430, Khyber Pakhtunkhwa (KPK), Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"354","DOI":"10.4103\/0970-2113.102824","article-title":"Digital clubbing","volume":"29","author":"Sarkar","year":"2012","journal-title":"Lung India"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ajhg.2011.11.019","article-title":"Exome sequencing identifies SLCO2A1 mutations as a cause of primary hypertrophic osteoarthropathy","volume":"90","author":"Zhang","year":"2012","journal-title":"Am. 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