Missense mutations have unexpected consequences: The McArdle disease paradigm

Autor: Garcia-Consuegra, I, Asensio-Pena, S, Ballester-Lopez, A, Francisco-Velilla, R, Pinos, T, Pintos-Morell, G, Coll-Canti, J, Gonzalez-Quintana, A, Andreu, AL, Arenas, J, Lucia, A, Nogales-Gadea, G, Martin, MA
Rok vydání: 2018
Předmět:
Zdroj: Human Mutation
r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol
instname
ISSN: 1059-7794
Popis: McArdle disease is a disorder of muscle glycogen metabolism caused by mutations in the PYGM gene, encoding for the muscle-specific isoform of glycogen phosphorylase (M-GP). The activity of this enzyme is completely lost in patients' muscle biopsies, when measured with a standard biochemical test which, does not allow to determine M-GP protein levels. We aimed to determine M-GP protein levels in the muscle of McArdle patients, by studying biopsies of 40 patients harboring a broad spectrum of PYGM mutations and 22 controls. Lack of M-GP protein was found in muscle in the vast majority (95%) of patients, irrespective of the PYGM genotype, including those carrying missense mutations, with few exceptions. M-GP protein biosynthesis is not being produced by PYGM mutations inducing premature termination codons (PTC), neither by most PYGM missense mutations. These findings explain the lack of PYGM genotype-phenotype correlation and have important implications for the design of molecular-based therapeutic approaches.
Databáze: OpenAIRE
Externí odkaz: