title: Gene expression profiling in dysferlinopathies using a dedicated muscle microarray.
abstract: We have performed expression profiling to define the molecular changes in dysferlinopathy using a novel dedicated microarray platform made with 3'-end skeletal muscle cDNAs. Eight dysferlinopathy patients, defined by western blot, immunohistochemistry and mutation analysis, were investigated with this technology. In a first experiment RNAs from different limb-girdle muscular dystrophy type 2B patients were pooled and compared with normal muscle RNA to characterize the general transcription pattern of this muscular disorder. Then the expression profiles of patients with different clinical traits were independently obtained and hierarchical clustering was applied to discover patient-specific gene variations. MHC class I genes and genes involved in protein biosynthesis were up-regulated in relation to muscle histopathological features. Conversely, the expression of genes codifying the sarcomeric proteins titin, nebulin and telethonin was down-regulated. Neither calpain-3 nor caveolin, a sarcolemmal protein interacting with dysferlin, was consistently reduced. There was a major up-regulation of proteins interacting with calcium, namely S100 calcium-binding proteins and sarcolipin, a sarcoplasmic calcium regulator.
authors.affiliation: CRIBI Biotechnology Centre and Dipartimento di Biologia, Università degli Studi di Padova, Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Campanaro
authors.forename: Chiara
authors.initials: C
authors.lastname: Romualdi
authors.forename: Marina
authors.initials: M
authors.lastname: Fanin
authors.forename: Barbara
authors.initials: B
authors.lastname: Celegato
authors.forename: Beniamina
authors.initials: B
authors.lastname: Pacchioni
authors.forename: Silvia
authors.initials: S
authors.lastname: Trevisan
authors.forename: Paolo
authors.initials: P
authors.lastname: Laveder
authors.forename: Cristiano
authors.initials: C
authors.lastname: De Pittà
authors.forename: Elena
authors.initials: E
authors.lastname: Pegoraro
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Valle
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.forename: Gerolamo
authors.initials: G
authors.lastname: Lanfranchi
mesh_terms: D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000378:metabolism; D002648:Child; D000073939:Dysferlin; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D032342:Muscle Cells / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D002118:Calcium