Clinical, imaging, morphologic, and molecular features of X-linked VMA21-related myopathy in two unrelated Brazilian families

Cotta, Ana; Carvalho, Elmano; da-Cunha-Júnior, Antonio Lopes; Navarro, Monica M.; Menezes, Miriam Melo; Paim, Júlia Filardi; Valicek, Jaquelin; Lima, Maria Isabel; Velloso-Filho, Roberto; Freire-Lyra, Maria Henriqueta; Takata, Reinaldo Issao; Inoue, Michio; Okubo, Mariko; Iida, Aritoshi; Nishino, Ichizo

doi:10.1016/j.jns.2020.116977

Cited by 3 publications

(4 citation statements)

References 6 publications

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“…1 16 However, selective involvement of peripheral vastus lateralis, partial rectus femoris, and peripheral tibialis anterior muscle has also recently been described. 11 Our patient also had typical findings as described in previous reports with fatty infiltration of the vasti and adductor magnus and sparing of rectus femoris, showing that imaging pattern could be a strong indicator toward XMEA diagnosis in clinically suspected patients.…”

Section: Discussionsupporting

confidence: 87%

“…Though there are many case reports from Europe and America, there are only a few cases from Asia (Comparison with previous studies is given in ►Table 1). 1,3-5, [7][8][9][10][11][12][13][14][15][16][17] XMEA affects males and has a slowly progressive proximal limb muscle weakness and normal cardiac function with onset ranging from childhood to adulthood. 10 VMA21 is an assembly chaperone for the principal mammalian proton pump required for lysosome acidification.…”

Section: Discussionmentioning

confidence: 99%

“…Though there are many case reports from Europe and America, there are only a few cases from Asia (Comparison with previous studies is given in Table 1 ). 1 3 4 5 7 8 9 10 11 12 13 14 15 16 17…”

Section: Discussionmentioning

confidence: 99%

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Identification of a Novel Intronic Mutation in VMA21 Associated with a Classical Form of X-Linked Myopathy with Autophagy

Bardhan,

Polavarapu,

Baskar

et al. 2024

Glob Med Genet

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Introduction VMA21-related myopathy is one of the rare forms of slowly progressive myopathy observed in males. Till now, there have been only a handful of reports, mainly from Europe and America, and two reports from India. Method Here, we describe a case of genetically confirmed VMA21-associated myopathy with clinical, histopathological, and imaging features with a list of known VMA21 mutations. Results A 29-year-old man had the onset of symptoms at 18 years of age with features of proximal lower limb weakness. Muscle magnetic resonance imaging showed the preferential involvement of vasti and adductor magnus. A biopsy of the left quadriceps femoris showed features of autophagic vacuolar myopathy with vacuoles containing granular eosinophilic materials. In targeted next-generation sequencing, hemizygous mutation in the 3′ splice site of intron 2 of the VMA21 gene (c.164–7 T > A) was identified and confirmed the diagnosis of X-linked myopathy with excessive autophagy. Conclusion This report expands the phenotypic and genotypic profile of VMA21-related myopathy, with a yet unreported mutation in India.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Identification of a Novel Intronic Mutation in VMA21 Associated with a Classical Form of X-Linked Myopathy with Autophagy

Bardhan,

Polavarapu,

Baskar

et al. 2024

Glob Med Genet

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“…VMA21 mutations have mainly been identified in introns. Some affect the splicing branch point (c.54-27A>C; c.54-27A>T; c.54-16_54-8del) [ 4 ], some affect the splicing donor site (c.163 + 4A>G) [ 4 , 5 ], and some affect the splicing acceptor site (c.164-6T>G; c.164-7T>G) [ 4 , 6 , 7 , 8 ]. Only one mutation was identified in an exon (c.272G>C), but this point mutation was predicted to affect a splice-enhancer site [ 4 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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

Pégat

Streichenberger

Lacoste

et al. 2022

Genes

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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.

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Phenotype variability and natural history of X-linked myopathy with excessive autophagy

Fernández-Eulate,

Alfieri,

Spinazzi

et al. 2024

J Neurol

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Clinical, imaging, morphologic, and molecular features of X-linked VMA21-related myopathy in two unrelated Brazilian families

Cited by 3 publications

References 6 publications

Identification of a Novel Intronic Mutation in VMA21 Associated with a Classical Form of X-Linked Myopathy with Autophagy

Identification of a Novel Intronic Mutation in VMA21 Associated with a Classical Form of X-Linked Myopathy with Autophagy

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

Phenotype variability and natural history of X-linked myopathy with excessive autophagy

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