{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:39:21Z","timestamp":1790908761655,"version":"4.1.0"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,10,26]]},"abstract":"<jats:p>Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disorder characterized by an insidious onset and progressive course. The disease has a frequency of about 1 in 20,000 and is transmitted in an autosomal dominant fashion with almost complete penetrance. Deletion of an integral number of tandemly arrayed 3.3-kb repeat units (D4Z4) on chromosome 4q35 is associated with FSHD but otherwise the molecular basis of the disease and its pathophysiology remain obscure. Comparison of mRNA populations between appropriate cell types can facilitate identification of genes relevant to a particular biological or pathological process. In this report, we have compared mRNA populations of FSHD and normal muscle. Unexpectedly, the dystrophic muscle displayed profound alterations in gene expression characterized by severe underexpression or overexpression of specific mRNAs. Intriguingly, many of the deregulated mRNAs are muscle specific. Our results suggest that a global misregulation of gene expression is the underlying basis for FSHD, distinguishing it from other forms of muscular dystrophy. The experimental approach used here is applicable to any genetic disorder whose pathogenic mechanism is incompletely understood.<\/jats:p>","DOI":"10.1073\/pnas.96.22.12650","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"12650-12654","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":34,"title":["Profound misregulation of muscle-specific gene expression in facioscapulohumeral muscular dystrophy"],"prefix":"10.1073","volume":"96","author":[{"given":"Rossella","family":"Tupler","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Suite 309, Worcester, MA 01605; Biologia Generale e Genetica Medica, Universita\u2019 degli Studi di Pavia, via Forlanini 14, 27100 Pavia, Italy; and Istituto di Fisiologia Umana, Universita\u2019 degli Studi di Pavia, via Forlanini 6, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Perini","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Suite 309, Worcester, MA 01605; Biologia Generale e Genetica Medica, Universita\u2019 degli Studi di Pavia, via Forlanini 14, 27100 Pavia, Italy; and Istituto di Fisiologia Umana, Universita\u2019 degli Studi di Pavia, via Forlanini 6, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonietta","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Suite 309, Worcester, MA 01605; Biologia Generale e Genetica Medica, Universita\u2019 degli Studi di Pavia, via Forlanini 14, 27100 Pavia, Italy; and Istituto di Fisiologia Umana, Universita\u2019 degli Studi di Pavia, via Forlanini 6, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Green","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Suite 309, Worcester, MA 01605; Biologia Generale e Genetica Medica, Universita\u2019 degli Studi di Pavia, via Forlanini 14, 27100 Pavia, Italy; and Istituto di Fisiologia Umana, Universita\u2019 degli Studi di Pavia, via Forlanini 6, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,10,26]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"1220","volume-title":"Myology","author":"Munsat T L","year":"1994","unstructured":"T L Munsat Myology, eds A G Engel, B Q Banker (McGraw\u2013Hill, New York), pp. 1220\u20131232 (1994)."},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1136\/jmg.26.12.755","volume":"26","author":"Lunt P W","year":"1992","unstructured":"P W Lunt, P S Harper J Med Genet 26, 755\u2013760 (1992).","journal-title":"J Med Genet"},{"key":"e_1_3_4_3_2","first-page":"424","volume":"51","author":"Gilbert J R","year":"1992","unstructured":"J R Gilbert, J M Stajich, M C Speer, J M Vance, C S Stewart, L H Yamaoka, F M Samson, M Fardeau, T G Potter, A D Roses, M A Pericak-Vance Am J Hum Genet 51, 424\u2013427 (1992).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_4_4_2","first-page":"428","volume":"51","author":"Mathews K D","year":"1992","unstructured":"K D Mathews, K A Mills, E P Bosch, V V Ionasescu, K R Wiles, K H Buetow, J C Murray Am J Hum Genet 51, 428\u2013431 (1992).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_4_5_2","first-page":"416","volume":"51","author":"Weiffenbach B","year":"1992","unstructured":"B Weiffenbach, R Bagley, K Falls, C Hyser, D Storvick, P Schultz, J Mendell, K W van Dijk, E C B Milner, R Griggs Am J Hum Genet 51, 416\u2013423 (1992).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_4_6_2","first-page":"396","volume":"51","author":"Sarfarazi M","year":"1992","unstructured":"M Sarfarazi, C Wijmenga, M Upadhyaya, B Weiffenbach, C Hyser, K D Mathews, J C Murray, J R Gilbert, M A Pericak-Vance, P Lunt, et al. Am J Hum Genet 51, 396\u2013403 (1992).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/ng0992-26","volume":"2","author":"Wijmenga C","year":"1992","unstructured":"C Wijmenga, J E Hewitt, L A Sandkuijl, L N Clark, T J Wright, G H Dauwerse, A Gruter, M H Hofker, P Moerer, R Williamson, et al. Nat Genet 2, 26\u201330 (1992).","journal-title":"Nat Genet"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF01553323","volume":"2","author":"Winokur S T","year":"1994","unstructured":"S T Winokur, U Bengtsson, J Feddersen, K D Mathews, B Weiffenbach, H Bailey, R P Markovich, J C Murray, J J Wasmuth, M R Altherr, et al. Chromosome Res 2, 225\u2013234 (1994).","journal-title":"Chromosome Res"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/dvg.1020150606","volume":"15","author":"Moehrle A","year":"1994","unstructured":"A Moehrle, R Paro Dev Genet 15, 478\u2013484 (1994).","journal-title":"Dev Genet"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1093\/hmg\/4.suppl_1.1765","volume":"4","author":"Hendrich B D","year":"1995","unstructured":"B D Hendrich, H F Willard Hum Mol Genet 4, 1765\u20131777 (1995).","journal-title":"Hum Mol Genet"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1093\/hmg\/3.8.1287","volume":"3","author":"Hewitt J E","year":"1994","unstructured":"J E Hewitt, R Lyle, L N Clark, E M Valleley, T J Wright, C Wijmenga, J C van Deutekom, F Francis, P T Sharpe, M Hofker, et al. Hum Mol Genet 3, 1287\u20131295 (1994).","journal-title":"Hum Mol Genet"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1002\/mus.880181304","volume":"2","author":"Lee J H","year":"1995","unstructured":"J H Lee, K Goto, C Matsuda, K Arahata Muscle Nerve 2, S6\u2013S13 (1995).","journal-title":"Muscle Nerve"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1006\/geno.1995.1166","volume":"28","author":"Lyle R","year":"1995","unstructured":"R Lyle, T J Wright, N L Clark, J E Hewitt Genomics 28, 389\u2013397 (1995).","journal-title":"Genomics"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1126\/science.279.5356.1544","volume":"279","author":"Morris M E","year":"1998","unstructured":"M E Morris, N Viswanathan, S Kuhlman, F Davis, C J Weitz Science 279, 1544\u20131547 (1998).","journal-title":"Science"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1126\/science.8438152","volume":"259","author":"Lisitsyn N","year":"1993","unstructured":"N Lisitsyn, N Lisitsyn, M Wigler Science 259, 946\u2013951 (1993).","journal-title":"Science"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1093\/nar\/26.4.1116","volume":"26","author":"Kuang W W","year":"1998","unstructured":"W W Kuang, D A Thompson, R V Hoch, R J Weigel Nucleic Acids Res 26, 1116\u20131123 (1998).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"6025","DOI":"10.1073\/pnas.93.12.6025","volume":"93","author":"Diatchenko L","year":"1996","unstructured":"L Diatchenko, Y-F C Lau, A P Campbell, A Chenchik, F Moqadam, B Huang, S Lukyanov, K Lukyanov, N Gurskaya, E D Sverdlov, P D Siebert Proc Natl Acad Sci USA 93, 6025\u20136030 (1996).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1136\/jmg.35.9.778","volume":"35","author":"Tupler R","year":"1998","unstructured":"R Tupler, L Barbierato, M Memmi, C A Sewry, D De Grandis, P Maraschio, L Tiepolo, A Ferlini J Med Genet 35, 778\u2013783 (1998).","journal-title":"J Med Genet"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"5463","DOI":"10.1073\/pnas.74.12.5463","volume":"74","author":"Sanger F","year":"1977","unstructured":"F Sanger, S Nicklen, A R Coulson Proc Natl Acad Sci USA 74, 5463\u20135467 (1977).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","volume":"215","author":"Altschul S F","year":"1990","unstructured":"S F Altschul, W Gish, W Miller, W Myers, D J Lipman J Mol Biol 215, 403\u2013410 (1990).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/sj.leu.2401274","volume":"13","author":"Hung H L","year":"1999","unstructured":"H L Hung, F Song, A Gewirtz Leukemia 13, 295\u2013297 (1999).","journal-title":"Leukemia"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/0003-2697(83)90551-1","volume":"129","author":"Giulian G G","year":"1983","unstructured":"G G Giulian, R L Moss, M Greaser Anal Biochem 129, 277\u2013287 (1983).","journal-title":"Anal Biochem"},{"key":"e_1_3_4_23_2","first-page":"1133","volume-title":"Myology","author":"Engel A G","year":"1994","unstructured":"A G Engel, M Yamamoto, K H Fischbeck Myology, eds A G Engel, B Q Banker (McGraw\u2013Hill, New York), pp. 1133\u20131187 (1994)."},{"key":"e_1_3_4_24_2","first-page":"1854","volume-title":"Myology","author":"Winderbank A J","year":"1994","unstructured":"A J Winderbank, D W Mulder Myology, eds A G Engel, B Q Banker (McGraw\u2013Hill, New York), pp. 1854\u20131869 (1994)."},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1101\/gad.9.16.1978","volume":"9","author":"Paranjape S M","year":"1995","unstructured":"S M Paranjape, A Krumm, J T Kadonaga Genes Dev 9, 1978\u20131991 (1995).","journal-title":"Genes Dev"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/S0092-8674(00)80154-3","volume":"86","author":"Roest H P","year":"1996","unstructured":"H P Roest, J van Klaveren, J de Wit, C G van Gurp, M H M Koken, M Vermey, J H van Roijen, J W Hoogerbrugge, J T M Vreeburg, W M Baarends, et al. Cell 86, 799\u2013810 (1996).","journal-title":"Cell"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/S0960-9822(98)70040-5","volume":"8","author":"Verrault A","year":"1997","unstructured":"A Verrault, P D Kaufman, R Kobayashi, B Stillman Curr Biol 8, 96\u2013108 (1997).","journal-title":"Curr Biol"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1126\/science.276.5317.1404","volume":"276","author":"Lin Q","year":"1997","unstructured":"Q Lin, J Schwarz, C Bucana, E N Olson Science 276, 1404\u20131407 (1997).","journal-title":"Science"}],"updated-by":[{"DOI":"10.1073\/pnas.97.5.2397-a","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2000,2,29]],"date-time":"2000-02-29T00:00:00Z","timestamp":951782400000}}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.96.22.12650","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:20:23Z","timestamp":1654561223000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.96.22.12650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,10,26]]},"references-count":28,"journal-issue":{"issue":"22","published-print":{"date-parts":[[1999,10,26]]}},"alternative-id":["10.1073\/pnas.96.22.12650"],"URL":"https:\/\/doi.org\/10.1073\/pnas.96.22.12650","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,10,26]]},"assertion":[{"value":"1999-01-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-08-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-10-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}