Point mutations in Czech DMD/BMD patients and their phenotypic outcome
| Autor: | Josef Zamecnik, Tat’ána Maříková, Jana Sedláčková, Lenka Fajkusová, Petr Vondráček, Markéta Hermanová, Josef Kraus, Zuzana Hrubá, Petra Hedvicakova, Jana Haberlová, Stanislav Voháňka |
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| Rok vydání: | 2009 |
| Předmět: |
Male
musculoskeletal diseases congenital hereditary and neonatal diseases and abnormalities Duchenne muscular dystrophy DNA Mutational Analysis Molecular Sequence Data Nonsense mutation Nonsense-mediated decay Biology medicine.disease_cause Dystrophin 03 medical and health sciences Exon 0302 clinical medicine Gene duplication medicine Humans Point Mutation RNA Messenger Genetics (clinical) Czech Republic 030304 developmental biology Genetics 0303 health sciences Mutation Base Sequence Point mutation Exons medicine.disease Molecular biology Muscular Dystrophy Duchenne Phenotype Neurology Pediatrics Perinatology and Child Health biology.protein Female Neurology (clinical) 030217 neurology & neurosurgery |
| Zdroj: | Neuromuscular Disorders. 19:749-753 |
| ISSN: | 0960-8966 |
| Popis: | Duchenne and Becker muscular dystrophies (DMD/BMD) are associated with mutations in the DMD gene. We determined the mutation status of 47 patients with dystrophinopathy without deletion or duplication in the DMD gene by screening performed by reverse transcription-PCR, protein truncation test, and DNA sequencing. We describe three patients with a mutation creating a premature termination codon (p.E55X, p.E1110X, and p.S3497PfsX2) but with a mild phenotype, which present three different ways of rescuing the DMD phenotype. In one patient we detected the insertion of a repetitive sequence AluYa5 in intron 56, which led to skipping of exon 57. Further, using quantitative analysis of DMD mRNA carrying various mutated alleles, we examine levels of mRNA degradation due to nonsense mediated mRNA decay. The quantity of dystrophin mRNA is different depending on the presence of a mutation leading to a premature termination codon, and position of the analysed mRNA region with respect to its 5′ end or 3′ end. Average relative amounts of DMD mRNAs carrying a premature termination codon is 48% and 17%, when using primers amplifying the 5′ and 3′ cDNA regions, respectively. |
| Databáze: | OpenAIRE |
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