Abstract
Desminopathies (MIM*601419) are clinically heterogeneous, manifesting with myopathy and/or cardiomyopathy and with intra-sarcoplasmic desmin-positive deposits. They have either an autosomal dominant (AD) or recessive (AR) pattern of inheritance. Desmin is a crucial intermediate filament protein regulating various cellular functions in muscle cells. Here, we report a 13-year-old girl, born of second-degree consanguineous parents, with normal developmental milestones, who presented with dilated cardiomyopathy, respiratory insufficiency and predominant distal upper limb weakness. A striking feature on muscle biopsy was the presence of a peripheral chain of nuclei in addition to myopathic features. Immunostaining showed complete lack of desmin expression, further confirmed by western blot analysis. Ultrastructurally, subsarcolemmal granular material, expanded Z-band aggregation, distortion of myofilaments, focal Z-band streaming, lobed and clustered myonuclei were observed. Next-generation sequencing revealed a novel homozygous nonsense mutation c.448C>T, p.R150X in the patient, while the parents were heterozygous carriers. Single mitochondrial DNA deletion and isolated complex IV deficiency were noted. Our findings add to the ever-expanding phenotype and molecular spectrum of desminopathies.
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Acknowledgements
We are thankful to the patient and her parents for participating in this study. We also thank the Department of Science and Technology, Govt. of India, for financial assistance.
Funding
Financial assistance was received from Department of Science and Technology [DSTRef No. F. NO.SR/SO/HS-103/2009/1(G) dated 8th Sept 2011], Govt. of India.
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Study concept and design: RS, GN; Data Acquisition: RS, VP, KP, DR, SC, KS, SV, SN, MF, AJ, NA, GN; Data analysis and interpretation: RS, VP, KP, DR, KS, MF, AJ, NA, GN; manuscript drafting: RS, GN; Critical revision for intellectual content: RS, KS, NA, GN.
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The study was approved by Institute Ethical Committee (NIMHANS IEC NO. Sl.No.1, Clinical Neurosciences) and written informed consent was taken from the participants.
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Santhoshkumar, R., Preethish-Kumar, V., Polavarapu, K. et al. A Novel L1 Linker Mutation in DES Resulted in Total Absence of Protein. J Mol Neurosci 71, 2468–2473 (2021). https://doi.org/10.1007/s12031-021-01856-0
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DOI: https://doi.org/10.1007/s12031-021-01856-0