{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:26:15Z","timestamp":1762867575432,"version":"3.37.3"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,10,30]],"date-time":"2018-10-30T00:00:00Z","timestamp":1540857600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,10,30]],"date-time":"2018-10-30T00:00:00Z","timestamp":1540857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Systemic sclerosis (SSc) is a prototypic systemic fibrotic disease with unclearly characterized genetic basis. We have discovered that mutations in family with sequence similarity 111, member B (<jats:italic>FAM111B<\/jats:italic>) gene cause hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis, a multisystem fibrotic condition with clinical similarities to SSc. This observation has established <jats:italic>FAM111B<\/jats:italic> as a candidate gene for SSc. Patients and Methods: Demographic and clinical characteristics of consenting adults with definite SSc were recorded. Blood DNA analysis was performed using the High-Resolution Melt technique, and samples with abnormal electropherograms were selected for Sanger sequencing to identify mutations. Ethnically-matched controls from the general South African population were used to verify the frequency of variants in <jats:italic>FAM111B<\/jats:italic>. Public databases such as 1000 Genomes and ExAC were also used to verify the frequency of variants in FAM111B. Results: Of 131 patients, 118 (90.1%) were female, and 78 (59.5%) were black Africans. Genetic analysis revealed two <jats:italic>FAM111B<\/jats:italic> genetic variants. The c.917\u2009A\u2009&gt;\u2009G variant (rs200497516) was found in one SSc patients, and one control, and was classified as a missense variant of unknown significance. The c.988\u2009C\u2009&gt;\u2009T variant (rs35732637) occurred in three SSc patients and 42\/243 (17.3%) of healthy controls, and is a known polymorphism. Conclusion: One rare variant was found in a patient with SSc but has no functional or structural impact on the <jats:italic>FAM111B<\/jats:italic> gene. In this cohort, <jats:italic>FAM111B<\/jats:italic> gene mutations are not associated with SSc.<\/jats:p>","DOI":"10.1038\/s41598-018-34341-7","type":"journal-article","created":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T09:15:54Z","timestamp":1540372554000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mutations of FAM111B gene are not associated with Systemic Sclerosis"],"prefix":"10.1038","volume":"8","author":[{"given":"A.","family":"Gcelu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Deshpande","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Shaboodien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. F.","family":"Spracklen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Kalla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Tikly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6641-8950","authenticated-orcid":false,"given":"B. M.","family":"Mayosi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Hodkinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,10,30]]},"reference":[{"key":"34341_CR1","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1007\/s11926-014-0411-1","volume":"16","author":"T Akter","year":"2014","unstructured":"Akter, T., Silver, R. M. & Bogatkevich, G. S. Recent advances in understanding the pathogenesis of scleroderma-interstitial lung disease. Curr Rheumatol Rep 16, 411, https:\/\/doi.org\/10.1007\/s11926-014-0411-1 (2014).","journal-title":"Curr Rheumatol Rep"},{"key":"34341_CR2","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1183\/09059180.00005512","volume":"22","author":"JJ Solomon","year":"2013","unstructured":"Solomon, J. J. et al. Scleroderma lung disease. Eur Respir Rev 22, 6\u201319, https:\/\/doi.org\/10.1183\/09059180.00005512 (2013).","journal-title":"Eur Respir Rev"},{"key":"34341_CR3","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1093\/rheumatology\/kev264","volume":"54","author":"M Manetti","year":"2015","unstructured":"Manetti, M. & Matucci-Cerinic, M. The new frontier in systemic sclerosis: from epigenetics to new treatments. 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