Novel Intronic Mutation in VMA21 Causing Severe Phenotype of X-Linked Myopathy with Excessive Autophagy-Case Report.

Autor: Pegat A; Service ENMG et Pathologies Neuromusculaires, Hôpital Neurologique P. Wertheimer, Hospices Civils de Lyon, 69500 Bron, France.; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, 69008 Lyon, France., Streichenberger N; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, 69008 Lyon, France.; Service d'anatomopathologie, Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon, 69500 Bron, France., Lacoste N; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, 69008 Lyon, France., Hermier M; Service de Neuroradiologie, Hôpital Neurologique P. Wertheimer, Hospices Civils de Lyon, 69500 Bron, France., Menassa R; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, 69008 Lyon, France.; Service de Biochimie et Biologie Moléculaire, Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon, 69500 Bron, France., Coudert L; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, 69008 Lyon, France., Theuriet J; Service ENMG et Pathologies Neuromusculaires, Hôpital Neurologique P. Wertheimer, Hospices Civils de Lyon, 69500 Bron, France.; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, 69008 Lyon, France., Froissart R; Service de Biochimie et Biologie Moléculaire, Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon, 69500 Bron, France., Terrone S; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, 69008 Lyon, France., Bouhour F; Service ENMG et Pathologies Neuromusculaires, Hôpital Neurologique P. Wertheimer, Hospices Civils de Lyon, 69500 Bron, France.; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, 69008 Lyon, France., Michel-Calemard L; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, 69008 Lyon, France.; Service de Biochimie et Biologie Moléculaire, Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon, 69500 Bron, France., Schaeffer L; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, 69008 Lyon, France.; Centre de Biotechnologie Cellulaire, CBC Biotec, Hospices Civils de Lyon-Groupement Est, 69500 Bron, France., Jacquier A; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, 69008 Lyon, France.; Centre de Biotechnologie Cellulaire, CBC Biotec, Hospices Civils de Lyon-Groupement Est, 69500 Bron, France.
Jazyk: angličtina
Zdroj: Genes [Genes (Basel)] 2022 Nov 29; Vol. 13 (12). Date of Electronic Publication: 2022 Nov 29.
DOI: 10.3390/genes13122245
Abstrakt: 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.
Databáze: MEDLINE
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