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CC BY 4.0 · Glob Med Genet 2024; 11(02): 167-174
DOI: 10.1055/s-0044-1786815
Original Article

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

Mainak Bardhan
1   Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, Karnataka, India
,
Kiran Polavarapu
2   Children's Hospital of Eastern Ontario Research Institute, Ottawa, K1H 5B2, Ontario, Canada
,
Dipti Baskar
1   Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, Karnataka, India
,
Veeramani Preethish-Kumar
1   Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, Karnataka, India
,
Seena Vengalil
1   Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, Karnataka, India
,
Saraswati Nashi
1   Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, Karnataka, India
,
Valakunja H. Ganaraja
1   Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, Karnataka, India
,
Dinesh Sharma
3   Deaprtment of Neuroradiology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, Karnataka, India
,
Karthik Kulanthaivelu
3   Deaprtment of Neuroradiology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, Karnataka, India
,
B.N. Nandeesh
4   Department of Neuropathology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, Karnataka, India
,
Atchayaram Nalini
1   Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, Karnataka, India
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Abstract

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.

Keywords

VMA21-related myopathy - autophagy - muscle MRI

Prior Publication

None.




Publication History

Article published online:
10 May 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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