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Pagina iniziale ricerca area autori guida all'uso sequence variants in the ryr1 gene and genetic diseases: malignant hyperthermia and congenital myopathies perrotta, giuseppa (2009) sequence variants in the ryr1 gene and genetic diseases: malignant hyperthermia and congenital myopathies. [tesi di dottorato] (inedito) full text disponibile come: preview pdf - richiede un editor pdf del tipo gsview, xpdf o adobe acrobat reader 2908kb abstract this phd thesis has been focused on the identification and functional characterization of sequence variants in the ryr1 gene, associated with malignant hyperthermia (mh) and some congenital myopathies (cms). Mh is an autosomal dominant pharmacogenetic disorder caused by an altered intracellular ca2+ homeostasis. This pathology shows a life treatening hypermetabolic crisis after administration of anaesthetics and/or depolarizing muscle relaxants. Mh is syntomatologic silent and until now the only sensitive and specific test for the diagnosis of mh is the in vitro contracture test (ivct), carried out on muscle byopsies. Mh presents wide genetic heterogeneity: six genetic loci associated with the mh suscettible phenotype (mhs) have been identified. In more than 70% of mhs patients the locus segregating with the pathology is mhs-1, where the ryr1 gene maps. viagra for sale cheap viagra cheap viagra online viagra without a doctor prescription viagra for sale generic viagra online buy viagra online buy cheap viagra http://medicaresupplementspecialists.com/pfz-where-to-buy-viagra-online-lf/ buy viagra The ryr1 gene codifies for the ryanodine receptor type 1 (ryr1), a calcium release channel localised in the sarco/endoplasmic reticulum (sr/er) membrane of skeletal muscle and b-lymphocytes. Cms are a heterogeneous group of inherited neuromuscular disorders characterized by hypotonia and muscle weakness, that usually present at birth or early childhood or rarely adulthood. Myophathies linked to ryr1 mutations are differentiated on the basis of the histopathological features in: core myopathies (central core disease, multiminicore disease, nemaline rod myopathy, and centronuclear myopathy), characterized histologically by central cores, multi-minicores, nemaline rods, central nuclei in muscle fibers, respectively; and others myopathies (congenital neuromuscular disease with uniform type 1 fibers, and congenital fiber-type disproportion myopathy) characterized histologically by the almost exclusive presence of type 1 muscle fiber and relative hypotrophy of type 1 muscle fibers, respectively. Great phenotypic and histopathological overlap and marked phenotypic variability are present in different myopathies. So far more than cc sequence variants have been identified in the ryr1 gene, but only 28 variants have been investigated for their functional effect and included in the guidelines for molecular genetic detection of mh susceptibility (www. Emhg. Org). In this study, the mutation analysis of the ryr1 gene was performed by denaturing high performance liquid chromatography (dhplc) and automatic sequencing in 24 mhs subjects, one ccd patient and one with minicores. 14 ryr1 gene sequence variants, an in-frame insertion variant and several known and novel polym.


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