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Frameshift mutation in SQSTM1 causes proximal myopathy with rimmed vacuoles: A case report

p62/Sequestosome-1 (SQSTM1) is a stress-inducible scaffold protein involved in multiple cellular processes, including apoptosis, inflammation, cell survival, and selective autophagy. SQSTM1 mutations are associated with a spectrum of multisystem proteinopathy, including Paget disease of the bone, am...

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Autores principales: Wu, Rui, Shao, Sai, Yin, Ling, Deng, Jianwen, Guo, Shougang, Lu, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043206/
https://www.ncbi.nlm.nih.gov/pubmed/36998782
http://dx.doi.org/10.3389/fneur.2023.1043136
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author Wu, Rui
Shao, Sai
Yin, Ling
Deng, Jianwen
Guo, Shougang
Lu, Lin
author_facet Wu, Rui
Shao, Sai
Yin, Ling
Deng, Jianwen
Guo, Shougang
Lu, Lin
author_sort Wu, Rui
collection PubMed
description p62/Sequestosome-1 (SQSTM1) is a stress-inducible scaffold protein involved in multiple cellular processes, including apoptosis, inflammation, cell survival, and selective autophagy. SQSTM1 mutations are associated with a spectrum of multisystem proteinopathy, including Paget disease of the bone, amyotrophic lateral sclerosis, frontotemporal dementia, and distal myopathy with rimmed vacuoles (MRV). Herein, we report a new phenotype of SQSTM1-associated proteinopathy, a novel frameshift mutation in SQSTM1 causing proximal MRV. A 44-year-old Chinese patient presented with progressive limb–girdle weakness. She had asymmetric proximal limb weakness and myopathic features on electromyography. The magnetic resonance images showed fatty infiltration into muscles, predominantly in the thighs and medial gastrocnemius, sparing the tibialis anterior. Muscle histopathology revealed abnormal protein deposition, p62/SQSTM1-positive inclusions, and rimmed vacuoles. Next-generation sequencing showed a novel pathogenic SQSTM1 frameshift mutation, c.542_549delACAGCCGC (p. H181Lfs(*)66). We expanded the pathogenic genotype of SQSTM1 to include a new, related phenotype: proximal MRV. We suggest that SQSTM1 variations should be screened in cases of proximal MRV.
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spelling pubmed-100432062023-03-29 Frameshift mutation in SQSTM1 causes proximal myopathy with rimmed vacuoles: A case report Wu, Rui Shao, Sai Yin, Ling Deng, Jianwen Guo, Shougang Lu, Lin Front Neurol Neurology p62/Sequestosome-1 (SQSTM1) is a stress-inducible scaffold protein involved in multiple cellular processes, including apoptosis, inflammation, cell survival, and selective autophagy. SQSTM1 mutations are associated with a spectrum of multisystem proteinopathy, including Paget disease of the bone, amyotrophic lateral sclerosis, frontotemporal dementia, and distal myopathy with rimmed vacuoles (MRV). Herein, we report a new phenotype of SQSTM1-associated proteinopathy, a novel frameshift mutation in SQSTM1 causing proximal MRV. A 44-year-old Chinese patient presented with progressive limb–girdle weakness. She had asymmetric proximal limb weakness and myopathic features on electromyography. The magnetic resonance images showed fatty infiltration into muscles, predominantly in the thighs and medial gastrocnemius, sparing the tibialis anterior. Muscle histopathology revealed abnormal protein deposition, p62/SQSTM1-positive inclusions, and rimmed vacuoles. Next-generation sequencing showed a novel pathogenic SQSTM1 frameshift mutation, c.542_549delACAGCCGC (p. H181Lfs(*)66). We expanded the pathogenic genotype of SQSTM1 to include a new, related phenotype: proximal MRV. We suggest that SQSTM1 variations should be screened in cases of proximal MRV. Frontiers Media S.A. 2023-03-14 /pmc/articles/PMC10043206/ /pubmed/36998782 http://dx.doi.org/10.3389/fneur.2023.1043136 Text en Copyright © 2023 Wu, Shao, Yin, Deng, Guo and Lu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Wu, Rui
Shao, Sai
Yin, Ling
Deng, Jianwen
Guo, Shougang
Lu, Lin
Frameshift mutation in SQSTM1 causes proximal myopathy with rimmed vacuoles: A case report
title Frameshift mutation in SQSTM1 causes proximal myopathy with rimmed vacuoles: A case report
title_full Frameshift mutation in SQSTM1 causes proximal myopathy with rimmed vacuoles: A case report
title_fullStr Frameshift mutation in SQSTM1 causes proximal myopathy with rimmed vacuoles: A case report
title_full_unstemmed Frameshift mutation in SQSTM1 causes proximal myopathy with rimmed vacuoles: A case report
title_short Frameshift mutation in SQSTM1 causes proximal myopathy with rimmed vacuoles: A case report
title_sort frameshift mutation in sqstm1 causes proximal myopathy with rimmed vacuoles: a case report
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043206/
https://www.ncbi.nlm.nih.gov/pubmed/36998782
http://dx.doi.org/10.3389/fneur.2023.1043136
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