A Novel L1 Linker Mutation in DES Resulted in Total Absence of Protein

Reghunathan, Dinesh and Chaudhari, Sima and Kapaettu, Satyamoorthy (2021) A Novel L1 Linker Mutation in DES Resulted in Total Absence of Protein. Journal of Molecular Neuroscience, 71. pp. 2468-2473. ISSN 0895-8696

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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 flament 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 insufciency 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 confrmed by western blot analysis. Ultrastructurally, subsarcolemmal granular material, expanded Z-band aggregation, distortion of myoflaments, 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 defciency were noted. Our fndings add to the ever-expanding phenotype and molecular spectrum of desminopathies

Item Type: Article
Uncontrolled Keywords: Desmin; L1 linker; Dilated cardiomyopathy; Cardio-skeletal phenotype
Subjects: Life Sciences > MLSC Manipal
Depositing User: KMC Library
Date Deposited: 28 Jan 2022 04:28
Last Modified: 28 Jan 2022 04:28
URI: http://eprints.manipal.edu/id/eprint/158020

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