Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations
| Autor: | Yakov Fellig, Zohar Argov, Leigh B. Waddell, Nicola Foulds, Alexander Lossos, Ingrid Mazanti, Nigel F. Clarke, Olayinka Raheem, Simon Hammans, Haider Katifi, Christopher Lindberg, Bjarne Udd, Anders Oldfors, Homa Tajsharghi, Richard Webster |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Biopsy DNA Mutational Analysis Nonsense mutation Mutation Missense Gene Expression Genes Recessive Biology Compound heterozygosity Article Muscular Diseases Myosin Genetics medicine Humans Missense mutation Genetic Predisposition to Disease Child Myopathy Genetics (clinical) Family Health Muscle Weakness Ophthalmoplegia Muscle biopsy Myosin Heavy Chains medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction Muscle weakness Skeletal muscle Middle Aged Molecular biology Pedigree 3. Good health medicine.anatomical_structure Codon Nonsense Muscle Fibers Fast-Twitch Female medicine.symptom |
| Zdroj: | European Journal of Human Genetics. 22:801-808 |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/ejhg.2013.250 |
| Popis: | Myosin myopathies comprise a group of inherited diseases caused by mutations in myosin heavy chain (MyHC) genes. Homozygous or compound heterozygous truncating MYH2 mutations have been demonstrated to cause recessive myopathy with ophthalmoplegia, mild-to-moderate muscle weakness and complete lack of type 2A muscle fibers. In this study, we describe for the first time the clinical and morphological characteristics of recessive myosin IIa myopathy associated with MYH2 missense mutations. Seven patients of five different families with a myopathy characterized by ophthalmoplegia and mild-to-moderate muscle weakness were investigated. Muscle biopsy was performed to study morphological changes and MyHC isoform expression. Five of the patients were homozygous for MYH2 missense mutations, one patient was compound heterozygous for a missense and a nonsense mutation and one patient was homozygous for a frame-shift MYH2 mutation. Muscle biopsy demonstrated small or absent type 2A muscle fibers and reduced or absent expression of the corresponding MyHC IIa transcript and protein. We conclude that mild muscle weakness and ophthalmoplegia in combination with muscle biopsy demonstrating small or absent type 2A muscle fibers are the hallmark of recessive myopathy associated with MYH2 mutations. |
| Databáze: | OpenAIRE |
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