دورية أكاديمية
Novel Intronic Mutation in VMA21 Causing Severe Phenotype of X-Linked Myopathy with Excessive Autophagy—Case Report
| العنوان: | Novel Intronic Mutation in VMA21 Causing Severe Phenotype of X-Linked Myopathy with Excessive Autophagy—Case Report |
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| المؤلفون: | Antoine Pegat, Nathalie Streichenberger, Nicolas Lacoste, Marc Hermier, Rita Menassa, Laurent Coudert, Julian Theuriet, Roseline Froissart, Sophie Terrone, Francoise Bouhour, Laurence Michel-Calemard, Laurent Schaeffer, Arnaud Jacquier |
| المصدر: | Genes, Vol 13, Iss 12, p 2245 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Genetics |
| مصطلحات موضوعية: | XMEA, VMA21, intronic mutation, intron retention, autophagy, vacuolar myopathy, Genetics, QH426-470 |
| الوصف: | X-linked Myopathy with Excessive Autophagy (XMEA) is a rare autophagic vacuolar myopathy caused by mutations in the Vacuolar ATPase assembly factor VMA21 gene; onset usually occurs during childhood and rarely occurs during adulthood. We described a 22-year-old patient with XMEA, whose onset was declared at 11 through gait disorder. He had severe four-limb proximal weakness and amyotrophy, and his proximal muscle MRC score was between 2 and 3/5 in four limbs; creatine kinase levels were elevated (1385 IU/L), and electroneuromyography and muscle MRI were suggestive of myopathy. Muscle biopsy showed abnormalities typical of autophagic vacuolar myopathy. We detected a hemizygous, unreported, intronic, single-nucleotide substitution c.164-20T>A (NM_001017980.4) in intron 2 of the VMA21 gene. Fibroblasts derived from this patient displayed a reduced level of VMA21 transcripts (at 40% of normal) and protein, suggesting a pathogenicity related to an alteration of the splicing efficiency associated with an intron retention. This patient with XMEA displayed a severe phenotype (rapid weakness of upper and lower limbs) due to a new intronic variant of VMA21, related to an alteration in the splicing efficiency associated with intron retention, suggesting that phenotype severity is closely related to the residual expression of the VMA21 protein. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2073-4425 96893389 |
| العلاقة: | https://www.mdpi.com/2073-4425/13/12/2245Test; https://doaj.org/toc/2073-4425Test |
| DOI: | 10.3390/genes13122245 |
| الوصول الحر: | https://doaj.org/article/61a1cdc3bf204edb968933896677a08fTest |
| رقم الانضمام: | edsdoj.61a1cdc3bf204edb968933896677a08f |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20734425 96893389 |
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| DOI: | 10.3390/genes13122245 |