{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T09:48:01Z","timestamp":1773827281366,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2005,2,23]],"date-time":"2005-02-23T00:00:00Z","timestamp":1109116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Extremely variable clinic and genetic features characterize mitochondrial encephalomyopathy (MEM). Pathogenic mitochondrial DNA (mtDNA) defects can be divided into large\u2010scale rearrangements and single point mutations. Clinical manifestations become evident when a threshold percentage of the total mtDNA is mutated. In some MEM, the \u201cmutant load\u201d in an affected tissue is directly related to the severity of the phenotype. However, the clinical phenotype is not simply a direct consequence of the relative abundance of mutated mtDNA. Other factors, such as nuclear background, can contribute to the disease process, resulting in a wide range of phenotypes caused by the same mutation. Using Affymetrix oligonucleotide cDNA microarrays (HG\u2010U133A), we studied the gene expression profile of muscle tissue biopsies obtained from 12 MEM patients [4 common 4977 bp deleted mtDNA and 8 A3243G: 4 progressive external ophthalmoplegia (PEO) and 4 mitochondrial myopathy, encephalopathy, lactic cidosis, and stroke\u2010like episodes syndrome (MELAS) phenotypes] compared with age\u2010matched healthy individuals. We found several differentially expressed genes: 35 were markedly up\u2010regulated in the mtDNA macro\u2010deletion group (vs. the control group) and 4 decreased; 56 genes were dysregulated in A3243G\u2010related disorders (53 down\u2010regulated in PEO and 3 up\u2010regulated in MELAS). Finally, 12 genes were similarly regulated in the majority of the MEM patients under study. Amongst these, we identified an increased expression of genes related to the metabolism of the amino groups, as well as of several genes involved in genetic information processing. Moreover, few genes were similarly decreased in MEM patients vs. the control group. Real\u2010time PCR demonstrated excellent reproducibility of the microarray\u2010based findings. The observed expression changes are likely to represent a molecular signature for mitochondrial disorders. Furthermore, the differential expression profile of MELAS\n                    <jats:sup>A3243G<\/jats:sup>\n                    vs. PEO\n                    <jats:sup>A3243G<\/jats:sup>\n                    may support a role of nuclear background in contributing to these different clinical phenotypes. MEM microarray data are available from GEO database (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/\">http:\/\/www.ncbi.nlm.nih.gov\/geo\/<\/jats:ext-link>\n                    ) with the accession number: GSE1462.\n                  <\/jats:p>","DOI":"10.1096\/fj.04-3045fje","type":"journal-article","created":{"date-parts":[[2005,2,23]],"date-time":"2005-02-23T20:24:55Z","timestamp":1109190295000},"page":"1-30","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Skeletal muscle gene expression profiling in mitochondrial disorders"],"prefix":"10.1096","volume":"19","author":[{"given":"Marco","family":"Crimi","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences University of Milan  20122 Milan"},{"name":"I.R.C.C.S. Ospedale Maggiore Policlinico \u201cDino Ferrari\u201d Center Center of Excellence for Neurodegenerative Diseases (CEND)  20122 Milan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreina","family":"Bordoni","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences University of Milan  20122 Milan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Menozzi","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. \u201cE. Medea \u2014 La Nostra Famiglia\u201d  23842 Bosisio Parini LC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Riva","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. \u201cE. Medea \u2014 La Nostra Famiglia\u201d  23842 Bosisio Parini LC"},{"name":"Department of Biomedical Engineering Polytechnic University  20133 Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Fortunate","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences University of Milan  20122 Milan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Galbiati","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences University of Milan  20122 Milan"},{"name":"I.R.C.C.S. Ospedale Maggiore Policlinico \u201cDino Ferrari\u201d Center Center of Excellence for Neurodegenerative Diseases (CEND)  20122 Milan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Del Bo","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences University of Milan  20122 Milan"},{"name":"I.R.C.C.S. Ospedale Maggiore Policlinico \u201cDino Ferrari\u201d Center Center of Excellence for Neurodegenerative Diseases (CEND)  20122 Milan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uberto","family":"Pozzoli","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. \u201cE. Medea \u2014 La Nostra Famiglia\u201d  23842 Bosisio Parini LC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nereo","family":"Bresolin","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences University of Milan  20122 Milan"},{"name":"I.R.C.C.S. Ospedale Maggiore Policlinico \u201cDino Ferrari\u201d Center Center of Excellence for Neurodegenerative Diseases (CEND)  20122 Milan"},{"name":"I.R.C.C.S. \u201cE. 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