Exon skipping in Duchenne Muscle dystrophy due to a silent p.Ser443= mutation in the DMD gene |
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| Affiliation: | 1. Department of Pediatrics, Division of Neuropediatrics, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen (FAU), Loschgestr. 15, 91054 Erlangen, Germany;2. Institute of Radiology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen (FAU), Erlangen, Germany;3. Medical Center of Human Genetics, Munich, Germany;4. Department of Pediatric Neurology and Developmental Medicine, Dr. v. Hauner Children''s Hospital, Ludwig-Maximilian-Universität Munich, Munich, Germany;1. Kids Neuroscience Centre, The Children''s Hospital at Westmead, Sydney, New South Wales 2145, Australia;2. Discipline of Child and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia;3. Department of Clinical Genetics, Children''s Hospital at Westmead, Sydney, New South Wales, Australia;4. Department of Diagnostic Genomics, PathWest Laboratory Medicine, QEII Medical Centre, Perth, Western Australia, Australia;5. Department of Neurology, Sydney Children''s Hospital, Sydney, New South Wales, Australia;6. Discipline of Paediatrics, School of Women''s and Children''s Health, UNSW Medicine, UNSW Sydney, New South Wales, Australia;7. Anatomical Pathology and Victorian Neuromuscular Laboratory Service, Alfred Health and Monash University, Australia;8. Centre for Clinical Genetics, Sydney Children''s Hospital, Sydney, New South Wales, Australia;9. Department of Neurology Royal Children''s Hospital, Murdoch Childrens Research Institute and University of Melbourne, Parkville, Victoria, Australia;10. Murdoch Childrens Research Institute, Melbourne, Victoria, Australia;1. Department of Human Genetics, University of Würzburg, Biozentrum Am Hubland, 97074 Würzburg, Germany;2. Children''s Hospital Cologne, Amsterdamerstraße 59, 50735 Cologne, Germany;3. Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, Children''s Hospital 1, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany |
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| Abstract: | Duchenne Muscle dystrophy (DMD) is a X-linked inherited disease predominantly caused by severe mutations in DMD gene leading to absence of dystrophin protein. Here we report a 14-year-old Mongolian boy suffering from proximal muscle weakness, pseudohypertrophic deltoid and gastrocnemius muscles since early childhood. Lactate dehydrogenase (LDH) and creatine kinase (CK) levels were elevated. Mutation analysis including MLPA and sequencing of the DMD gene revealed a hemizygous silent variant, c.1329C>T (p.Ser443=) in exon 11. This silent mutation, listed in the SNP database (rs1060502631), was described as a variant of unknown significance (VUS) in ClinVar database. cDNA analysis demonstrated partial skipping of exon 11 due to this mutation. Although silent mutations are usually considered non-pathogenic, our case emphasizes that silent mutations can be potentially pathogenic. Hence, if silent variants are not annotated in database or not known to be benign, they should be analysed further at cDNA level. |
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| Keywords: | Duchenne Muscle dystrophy (DMD) Exon-skipping Silent mutation Pathogen |
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