Several members of the sarcomeric myosin heavy chain (MHC) gene family have been mapped in the human genome but many of them have not yet been identified. In this study we report the identification of two human skeletal MHC genes as fast IIa and IIx MHC based on pattern of expression and sequence homology with the corresponding rat genes in the 3'-translated and untranslated regions. The distribution of these two gene products as well as that of the beta/slow MHC gene was analyzed in human skeletal muscles by in situ hybridization. The distribution of beta/slow, IIa, and IIx MHC transcripts defines three major muscle fiber types expressing a single MHC mRNA, i.e., either beta/slow, IIa, or IIx MHC mRNA, and two populations of hybrid fibers coexpressing beta/slow with IIa or IIa with IIx MHC mRNA. Fiber typing by ATPase histochemistry shows that IIa MHC transcripts are more abundant in histochemical type IIa fibers, whereas IIx MHC transcripts are more abundant in histochemical type IIb fibers.
"Three major isoforms are known in adult human limb muscle fibers: MyHC I, encoded by MYH7 and expressed in slow type I muscle fibers and in heart ventricles; MyHC IIa, encoded by MYH2 and expressed in fast type IIA muscle fibers, and MyHC IIx expressed in fast type IIB muscle fibers . To date pathogenetic mutations associated to hereditary myopathies have been identified in both MYH7 and MYH2 genes . The first pathogenetic MYH2 mutation, reported by Martinsson and coauthors in 2000 , was a dominant missense mutation in exon 17 (c.2116, "
[Show abstract][Hide abstract] ABSTRACT: Congenital myopathy related to mutations in myosin MyHC IIa gene (MYH2) is a rare neuromuscular disease. A single dominant missense mutation has been reported so far in a family in which the affected members had congenital joint contractures at birth, external ophthalmoplegia and proximal muscle weakness. Afterward only additional 4 recessive mutations have been identified in 5 patients presenting a mild non-progressive early-onset myopathy associated with ophthalmoparesis. We report a new de novo MYH2 missense mutation in a baby affected by a congenital myopathy characterized by severe dysphagia, respiratory distress at birth and external ophthalmoplegia. We describe clinical, histopathological and muscle imaging findings expanding the clinical and genetic spectrum of MYH2-related myopathy.
"There are several striated muscle MyHC isoforms encoded by different genes and expressed in a tissue and developmental specific manner [61–63, 84, 85]. In adult human limb skeletal muscle there are three major MyHC isoforms: MyHC I, also called slow/ß-cardiac MyHC, is encoded by MYH7 and is expressed in slow, type 1 muscle fibers as well as in the ventricles of the heart; MyHC IIa (MYH2) is expressed in fast, type 2A muscle fibers and MyHC IIx (MYH1) is expressed in fast, type 2B muscle fibers  (Table 1). The three different muscle fiber types differ in their contractile and physiological properties, which are partly determined by the different MyHCs. "
[Show abstract][Hide abstract] ABSTRACT: The myosin heavy chain (MyHC) is the molecular motor of muscle and forms the backbone of the sarcomere thick filaments. Different MyHC isoforms are of importance for the physiological properties of different muscle fiber types. Hereditary myosin myopathies have emerged as an important group of diseases with variable clinical and morphological expression depending on the mutated isoform and type and location of the mutation. Dominant mutations in developmental MyHC isoform genes (MYH3 and MYH8) are associated with distal arthrogryposis syndromes. Dominant or recessive mutations affecting the type IIa MyHC (MYH2) are associated with early-onset myopathies with variable muscle weakness and ophthalmoplegia as a consistent finding. Myopathies with scapuloperoneal, distal or limb-girdle muscle weakness including entities, such as myosin storage myopathy and Laing distal myopathy are the result of usually dominant mutations in the gene for slow/β cardiac MyHC (MYH7). Protein aggregation is part of the features in some of these myopathies. In myosin storage myopathy protein aggregates are formed by accumulation of myosin beneath the sarcolemma and between myofibrils. In vitro studies on the effects of different mutations associated with myosin storage myopathy and Laing distal myopathy indicate altered biochemical and biophysical properties of the light meromyosin, which is essential for thick filament assembly. Protein aggregates in the form of tubulofilamentous inclusions in association with vacuolated muscle fibers are present at late stage of dominant myosin IIa myopathy and sometimes in Laing distal myopathy. These protein aggregates exhibit features indicating defective degradation of misfolded proteins. In addition to protein aggregation and muscle fiber degeneration some of the myosin mutations cause functional impairment of the molecular motor adding to the pathogenesis of myosinopathies.
"Dall'osservazione dei preparati immunoistochimici per l'identificazione delle diverse isoforme dell'MHC nei muscoli oggetto di studio, in accordo con altri autori abbiamo rilevato sia per la specie Casertana sia per la specie Large White a 0 e 15gg che l'isoforma di tipo 2B non è stata localizzata e solo dopo i 30gg si notava la presenza di tale isoforma ma solo nella Large White (Fig. 13 -15). L'isoforma 2B, generalmente considerata tipica dei piccoli mammiferi e marsupiali (Zhong et al., 2001) non è espressa nei grandi mammiferi quali l'uomo (Smerdu et al., 1994), il cavallo (Serrano et al., 1996), il cane (Latorre et al., 1993), il babbuino ed il gatto (Lucas et al., 2000; Schiaffino e Reggiani, 1996), ma chiaramente espressa nei muscoli del maiale e risulta presente nelle fibre di maggior diametro e pertanto la sua presenza è correlata con la muscolarità, così come osservato nel nostro studio nei muscoli della Large "
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