Novel recessive myotilin mutation causes severe myofibrillar myopathy
| العنوان: | Novel recessive myotilin mutation causes severe myofibrillar myopathy |
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| المؤلفون: | Franz-Georg Hanisch, Benedikt Schoser, C. Kubny, Wolfram Kress, Elisa Bach, S. Feldkirchner, Stefan Müller, Joachim Schessl, Simone Rost |
| المصدر: | neurogenetics. 15:151-156 |
| بيانات النشر: | Springer Science and Business Media LLC, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Adult, Male, Genes, Recessive, Biology, Sarcomere, Cellular and Molecular Neuroscience, Exon, Genetics, medicine, Humans, Myotilin, Missense mutation, Connectin, Muscular dystrophy, Muscle, Skeletal, Myopathy, Genetics (clinical), Exome sequencing, Homozygote, Microfilament Proteins, Skeletal muscle, Exons, medicine.disease, Molecular biology, medicine.anatomical_structure, Mutation, medicine.symptom, Myopathies, Structural, Congenital |
| الوصف: | We identified the first homozygous and hence recessive mutation in the myotilin gene (MYOT) in a family affected by a severe myofibrillar myopathy (MFM). MFM is a rare, progressive and devastating disease of human skeletal muscle with distinct histopathological pattern of protein aggregates and myofibrillar degeneration. So far, only heterozygous missense mutations in MYOT have been associated with autosomal dominant myofibrillar myopathy, limb-girdle muscular dystrophy type 1A and distal myopathy. Myotilin itself is highly expressed in skeletal and cardiac muscle and is localized at the Z-disc and therefore interacts in sarcomere assembly. We performed whole-exome sequencing in a German family clinically diagnosed with MFM and identified a homozygous mutation in exon 2, c.16C > G (p.Arg6Gly). Using laser microdissection followed by quantitative mass spectrometry, we identified the myotilin protein as one component showing the highest increased abundance in the aggregates in the index patient. We suggest that the combined approach has a high potential as a new tool for the confirmation of unclassified variants which are found in whole-exome sequencing approaches. |
| تدمد: | 1364-6753 1364-6745 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::14f86d2c915b585ab9098c71eb5d0c63Test https://doi.org/10.1007/s10048-014-0410-4Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....14f86d2c915b585ab9098c71eb5d0c63 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13646753 13646745 |
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