{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T15:07:08Z","timestamp":1777648028445,"version":"3.51.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T00:00:00Z","timestamp":1449100800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T00:00:00Z","timestamp":1449100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hum Genet"],"published-print":{"date-parts":[[2016,4]]},"DOI":"10.1038\/jhg.2015.146","type":"journal-article","created":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T07:20:41Z","timestamp":1449127241000},"page":"307-316","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The African\u2212387 C>T TGFB1 variant is functional and associates with the ophthalmoplegic complication in juvenile myasthenia gravis"],"prefix":"10.1038","volume":"61","author":[{"given":"Melissa","family":"Nel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy-Mari","family":"Buys","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robyn","family":"Rautenbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaheen","family":"Mowla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Prince","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeannine M","family":"Heckmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,12,3]]},"reference":[{"key":"BFjhg2015146_CR1","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1196\/annals.1405.037","volume":"1132","author":"J Soltys","year":"2008","unstructured":"Soltys, J., Gong, B., Kaminski, H. J., Zhou, Y. & Kusner, L. L. Extraocular muscle susceptibility to myasthenia gravis: unique immunological environment? Ann. NY Acad. Sci. 1132, 220\u2013224 (2008).","journal-title":"Ann. NY Acad. Sci."},{"key":"BFjhg2015146_CR2","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.nmd.2007.07.002","volume":"17","author":"JM Heckmann","year":"2007","unstructured":"Heckmann, J. M., Owen, E. P. & Little, F. Myasthenia gravis in South Africans: racial differences in clinical manifestations. Neuromuscul. Disord. 17, 929\u2013934 (2007).","journal-title":"Neuromuscul. Disord."},{"key":"BFjhg2015146_CR3","doi-asserted-by":"publisher","first-page":"532","DOI":"10.7196\/SAMJ.5390","volume":"102","author":"JM Heckmann","year":"2012","unstructured":"Heckmann, J. M., Hansen, P., Van Toorn, R., Lubbe, E., Janse van Rensburg, E. & Wilmshurst, J. M. The characteristics of juvenile myasthenia gravis among South Africans. S. Afr. Med. J. 102, 532\u2013536 (2012).","journal-title":"S. Afr. Med. J."},{"key":"BFjhg2015146_CR4","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.4049\/jimmunol.142.8.2654","volume":"142","author":"G Biesecker","year":"1989","unstructured":"Biesecker, G. & Gomez, C. M. Inhibition of acute passive transfer experimental autoimmune myasthenia gravis with Fab antibody to complement C6. J. Immunol. 142, 2654\u20132659 (1989).","journal-title":"J. Immunol."},{"key":"BFjhg2015146_CR5","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1084\/jem.147.4.973","volume":"147","author":"VA Lennon","year":"1978","unstructured":"Lennon, V. A., Seybold, M. E., Lindstrom, J. M., Cochrane, C. & Ulevitch, R. Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis. J. Exp. Med. 147, 973\u2013983 (1978).","journal-title":"J. Exp. Med."},{"key":"BFjhg2015146_CR6","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1111\/j.1365-2249.2006.03205.x","volume":"146","author":"BP Morgan","year":"2006","unstructured":"Morgan, B. P., Chamberlain-Banoub, J., Neal, J. W., Song, W., Mizuno, M. & Harris, C. L. The membrane attack pathway of complement drives pathology in passively induced experimental autoimmune myasthenia gravis in mice. Clin. Exp. Immunol. 146, 294\u2013302 (2006).","journal-title":"Clin. Exp. Immunol."},{"key":"BFjhg2015146_CR7","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1097\/00005072-198003000-00005","volume":"39","author":"K Sahashi","year":"1980","unstructured":"Sahashi, K., Engel, A. G., Lambert, E. H. & Howard, F. M. Ultrastructural localization of the terminal and lytic ninth complement component (C9) at the motor end-plate in myasthenia gravis. J. Neuropathol. Exp. Neurol. 39, 160\u2013172 (1980).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"BFjhg2015146_CR8","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.expneurol.2006.06.003","volume":"202","author":"HJ Kaminski","year":"2006","unstructured":"Kaminski, H. J., Kusner, L. L., Richmonds, C., Medof, M. E. & Lin, F. Deficiency of decay accelerating factor and CD59 leads to crisis in experimental myasthenia. Exp. Neurol. 202, 287\u2013293 (2006).","journal-title":"Exp. Neurol."},{"key":"BFjhg2015146_CR9","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.expneurol.2004.06.005","volume":"189","author":"HJ Kaminski","year":"2004","unstructured":"Kaminski, H. J., Li, Z., Richmonds, C., Lin, F. & Medof, M. E. Complement regulators in extraocular muscle and experimental autoimmune myasthenia gravis. Exp. Neurol. 189, 333\u2013342 (2004).","journal-title":"Exp. Neurol."},{"key":"BFjhg2015146_CR10","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1172\/JCI0216086","volume":"110","author":"F Lin","year":"2002","unstructured":"Lin, F., Kaminski, H. J., Conti-Fine, B. M., Wang, W., Richmonds, C. & Medof, M. E. Markedly enhanced susceptibility to experimental autoimmune myasthenia gravis in the absence of decay-accelerating factor protection. J. Clin. Invest. 110, 1269\u20131274 (2002).","journal-title":"J. Clin. Invest."},{"key":"BFjhg2015146_CR11","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1084\/jem.160.5.1558","volume":"160","author":"ME Medof","year":"1984","unstructured":"Medof, M. E., Kinoshita, T. & Nussenzweig, V. Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. J. Exp. Med. 160, 1558\u20131578 (1984).","journal-title":"J. Exp. Med."},{"key":"BFjhg2015146_CR12","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jneuroim.2012.01.003","volume":"244","author":"J Soltys","year":"2012","unstructured":"Soltys, J., Halperin, J. & Xuebin, Q. DAF\/CD55 and Protectin\/CD59 modulate adaptive immunity and disease outcome in experimental autoimmune myasthenia gravis. J. Neuroimmunol. 244, 63\u201369 (2012).","journal-title":"J. Neuroimmunol."},{"key":"BFjhg2015146_CR13","doi-asserted-by":"publisher","first-page":"12062","DOI":"10.1073\/pnas.211257298","volume":"98","author":"JD Porter","year":"2001","unstructured":"Porter, J. D., Khanna, S., Kaminski, H. J., Rao, J. S., Merriam, P., Richmonds, C. R. et al. Extraocular muscle is defined by a fundamentally distinct gene expression profile. Proc. Natl Acad. Sci. USA 98, 12062\u201312067 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFjhg2015146_CR14","doi-asserted-by":"publisher","first-page":"4348","DOI":"10.1167\/iovs.14-14422","volume":"55","author":"Y Zhou","year":"2014","unstructured":"Zhou, Y., Kaminski, H. J., Gong, B., Cheng, G., Feuerman, J. M. & Kusner, L. RNA expression analysis of passive transfer myasthenia supports extraocular muscle as a unique immunological environment. Invest. Ophthalmol. Vis. Sci. 55, 4348\u20134359 (2014).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"BFjhg2015146_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/gene.2009.61","volume":"11","author":"JM Heckmann","year":"2010","unstructured":"Heckmann, J. M., Uwimpuhwe, H., Ballo, R., Kaur, M., Bajic, V. B. & Prince, S. A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis. Genes Immun. 11, 1\u201310 (2010).","journal-title":"Genes Immun."},{"key":"BFjhg2015146_CR16","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.nmd.2014.02.010","volume":"24","author":"J Auret","year":"2014","unstructured":"Auret, J., Abrahams, A., Prince, S. & Heckmann, J. M. The effects of prednisone and steroid-sparing agents on decay accelerating factor (CD55) expression: implications in myasthenia gravis. Neuromuscul. Disord. 24, 499\u2013508 (2014).","journal-title":"Neuromuscul. Disord."},{"key":"BFjhg2015146_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/2044-5040-1-19","volume":"1","author":"TN Burks","year":"2011","unstructured":"Burks, T. N. & Cohn, R. D. Role of TGF-\u03b2 signaling in inherited and acquired myopathies. Skelet. Muscle 1, 1\u201313 (2011).","journal-title":"Skelet. Muscle"},{"key":"BFjhg2015146_CR18","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1016\/S0002-9440(10)63188-4","volume":"164","author":"Y Li","year":"2004","unstructured":"Li, Y., Foster, W., Deasy, B. M., Chan, Y., Prisk, V., Tang, Y. et al. Transforming growth factor-beta1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: a key event in muscle fibrogenesis. Am. J. Pathol. 164, 1007\u20131019 (2004).","journal-title":"Am. J. Pathol."},{"key":"BFjhg2015146_CR19","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1002\/mus.22232","volume":"45","author":"CL Mendias","year":"2012","unstructured":"Mendias, C. L., Gumucio, J. P., Davis, M. E., Bromley, C. W., Davis, C. S. & Brooks, S. V. Transforming growth factor-beta induces skeletal muscle atrophy and fibrosis through the induction of atrogin-1 and scleraxis. Muscle Nerve 45, 55\u201359 (2012).","journal-title":"Muscle Nerve"},{"key":"BFjhg2015146_CR20","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1152\/physiolgenomics.00234.2004","volume":"24","author":"JD Porter","year":"2006","unstructured":"Porter, J. D., Israel, S., Gong, B., Merriam, A. P., Feuerman, J., Khanna, S. et al. Distinctive morphological and gene\/protein expression signatures during myogenesis in novel cell lines from extraocular and hindlimb muscle. Physiol. Genomics 24, 264\u2013275 (2006).","journal-title":"Physiol. Genomics"},{"key":"BFjhg2015146_CR21","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s00439-005-0112-y","volume":"119","author":"R Shah","year":"2006","unstructured":"Shah, R., Rahaman, B., Hurley, C. K. & Posch, P. E. Allelic diversity in the TGFB1 regulatory region: characterization of novel functional single nucleotide polymorphisms. Hum. Genet. 119, 61\u201374 (2006).","journal-title":"Hum. Genet."},{"key":"BFjhg2015146_CR22","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1002\/mus.24348","volume":"51","author":"B Mombaur","year":"2015","unstructured":"Mombaur, B., Lesosky, M. R., Liebenberg, L., Vreede, H. & Heckmann, J. M. Incidence of acetylcholine receptor-antibody-positive myasthenia gravis in South Africa. Muscle Nerve 51, 533\u2013537 (2015).","journal-title":"Muscle Nerve"},{"key":"BFjhg2015146_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2164-14-644","volume":"14","author":"A May","year":"2013","unstructured":"May, A., Hazelhurst, S., Li, Y., Norris, S., Govind, N., Tikly, M. et al. Genetic diversity in black South Africans from Soweto. BMC Genomics 14, 1\u201312 (2013).","journal-title":"BMC Genomics"},{"key":"BFjhg2015146_CR24","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","volume":"21","author":"JC Barrett","year":"2005","unstructured":"Barrett, J. C, Fry, B., Maller, J. & Daly, M. J. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263\u2013265 (2005).","journal-title":"Bioinformatics"},{"key":"BFjhg2015146_CR25","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1126\/science.1069424","volume":"296","author":"SB Gabriel","year":"2002","unstructured":"Gabriel, S. B., Schaffner, S. F., Nguyen, H., Moore, J. M., Roy, J., Blumenstiel, B. et al. The structure of haplotype blocks in the human genome. Science 296, 2225\u20132229 (2002).","journal-title":"Science"},{"key":"BFjhg2015146_CR26","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1086\/383251","volume":"74","author":"DR Nyholt","year":"2004","unstructured":"Nyholt, D. R. A simple correction for multiple testing for single-nucleotide polymorphisms in linage disequilibrium with each other. Am. J. Hum. Genet. 74, 765\u2013769 (2004).","journal-title":"Am. J. Hum. Genet."},{"key":"BFjhg2015146_CR27","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1002\/ijc.24526","volume":"125","author":"J Healy","year":"2009","unstructured":"Healy, J., Dionne, J., B\u00e9langer, H., Larivi\u00e8re, M., Beaulieu, P., Labuda, D. et al. Functional impact of sequence variation in the promoter region of TGFB1. Int. J. Cancer 125, 1483\u20131489 (2009).","journal-title":"Int. J. Cancer"},{"key":"BFjhg2015146_CR28","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s00439-006-0194-1","volume":"120","author":"R Shah","year":"2006","unstructured":"Shah, R., Hurley, C. K. & Posch, P. E. A molecular mechanism for the differential regulation of TGF-beta1 expression due to the common SNP \u2212509C-T (c. \u22121347C>T). Hum. Genet 120, 461\u2013469 (2006).","journal-title":"Hum. Genet"},{"key":"BFjhg2015146_CR29","doi-asserted-by":"publisher","first-page":"3817","DOI":"10.1210\/endo.142.9.8380","volume":"142","author":"GE Walker","year":"2001","unstructured":"Walker, G. E., Wilson, E. M., Powell, D. & Oh, Y. Butyrate, a histone deacetylase inhibitor, activates the human IGF binding protein-3 promoter in breast cancer cells: Molecular mechanism involves an Sp1\/Sp3 multiprotein complex. Endocrinology 142, 3817\u20133827 (2001).","journal-title":"Endocrinology"},{"key":"BFjhg2015146_CR30","doi-asserted-by":"publisher","first-page":"25742","DOI":"10.1074\/jbc.M102821200","volume":"276","author":"J Yang","year":"2001","unstructured":"Yang, J., Kawai, Y., Hanson, R. W. & Arinze, I. J. Sodium butyrate induces transcription from the G\u03b1i2 gene promoter through multiple Sp1 sites in the promoter and by activating the MEK-ERK signal transduction pathway. J. Biol. Chem. 276, 25742\u201325752 (2001).","journal-title":"J. Biol. Chem."},{"key":"BFjhg2015146_CR31","first-page":"495","volume":"4","author":"JA Barnard","year":"1993","unstructured":"Barnard, J. A. & Warwick, G. Butyrate rapidly induces growth inhibition and differentiation in HT-29 cells. Cell Growth Differ. 4, 495\u2013501 (1993).","journal-title":"Cell Growth Differ."},{"key":"BFjhg2015146_CR32","doi-asserted-by":"publisher","first-page":"4490","DOI":"10.1038\/onc.2012.480","volume":"32","author":"VR Skeen","year":"2012","unstructured":"Skeen, V. R., Collard, T. J., Southern, S. L., Greenhough, A., Hague, A., Townsend, P. A et al. BAG-1 suppresses expression of the key regulatory cytokine transforming growth factor \u03b2 (TGF-\u03b21) in colorectal tumour cells. Oncogene 32, 4490\u20134499 (2012).","journal-title":"Oncogene"},{"key":"BFjhg2015146_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13073-014-0092-4","volume":"6","author":"J Knight","year":"2014","unstructured":"Knight, J. Approaches for establishing the function of regulatory genetic variants involved in disease. Genome Med 6, 1\u201315 (2014).","journal-title":"Genome Med"},{"key":"BFjhg2015146_CR34","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1038\/nature08795","volume":"463","author":"SC Schuster","year":"2010","unstructured":"Schuster, S. C., Miller, W., Ratan, A., Tomsho, L. P., Giardine, B., Kasson, L. R. et al. Complete Khoisan and Bantu genomes from southern Africa. Nature 463, 943\u2013947 (2010).","journal-title":"Nature"},{"key":"BFjhg2015146_CR35","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1126\/science.1172257","volume":"324","author":"SA Tishkoff","year":"2009","unstructured":"Tishkoff, S. A., Reed, F. A., Friedlaender, F. R., Ehret, C., Ranciaro, A., Froment, A. et al. The genetic structure and history of Africans and African Americans. Science 324, 1035\u20131044 (2009).","journal-title":"Science"},{"key":"BFjhg2015146_CR36","doi-asserted-by":"publisher","first-page":"2485\u2009S","DOI":"10.1093\/jn\/133.7.2485S","volume":"133","author":"JR Davie","year":"2003","unstructured":"Davie, J. R. Inhibition of histone deacetylase activity by butyrate. J. Nutr. 133, 2485\u2009S\u20132493\u2009S (2003).","journal-title":"J. Nutr."},{"key":"BFjhg2015146_CR37","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/sj.ki.5000028","volume":"69","author":"N Matsumoto","year":"2006","unstructured":"Matsumoto, N., Riley, S., Fraser, D., Al-Assaf, S., Ishimura, E., Wolever, T. et al. Butyrate modulates TGF-\u03b21 generation and function: potential renal benefit for Acacia(sen) SUPERGUMTM (gum arabic)? Kidney Int. 69, 257\u2013265 (2006).","journal-title":"Kidney Int."},{"key":"BFjhg2015146_CR38","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1076\/ceyr.23.2.86.5478","volume":"23","author":"ET Cocuzzi","year":"2001","unstructured":"Cocuzzi, E. T., Bardenstein, D. S., Stavitsky, A., Sundarraj, N. & Medof, M. E. Upregulation of DAF (CD55) on orbital fibroblasts by cytokines. Differential effects of TNF-beta and TNF-alpha. Curr. Eye Res. 23, 86\u201392 (2001).","journal-title":"Curr. Eye Res."}],"container-title":["Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/jhg2015146.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/jhg2015146","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/jhg2015146.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T01:41:01Z","timestamp":1692150061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/jhg2015146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,3]]},"references-count":38,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["BFjhg2015146"],"URL":"https:\/\/doi.org\/10.1038\/jhg.2015.146","relation":{},"ISSN":["1434-5161","1435-232X"],"issn-type":[{"value":"1434-5161","type":"print"},{"value":"1435-232X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,3]]},"assertion":[{"value":"15 July 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2015","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2015","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}