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Multisystem proteinopathy: Where myopathy and motor neuron disease converge
Author(s) -
Korb Manisha K.,
Kimonis Virginia E.,
Mozaffar Tahseen
Publication year - 2021
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.27097
Subject(s) - amyotrophic lateral sclerosis , neurodegeneration , myopathy , frontotemporal dementia , stress granule , optineurin , biology , frontotemporal lobar degeneration , motor neuron , neuroscience , disease , phenotype , medicine , heterogeneous nuclear ribonucleoprotein , dementia , genetics , gene , pathology , ribonucleoprotein , rna , messenger rna , translation (biology)
Multisystem proteinopathy (MSP) is a pleiotropic group of inherited disorders that cause neurodegeneration, myopathy, and bone disease, and share common pathophysiology. Originally referred to as inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD), attributed to mutations in the gene encoding valosin‐containing protein (VCP), it has more recently been discovered that there are several other genes responsible for similar clinical and pathological phenotypes with muscle, brain, nerve, and bone involvement, in various combinations. These include heterogeneous nuclear ribonucleoprotein A2B1 and A1 ( hnRNPA2B1 , hnRNPA1 ), sequestosome 1 ( SQSTM1 ), matrin 3 ( MATR3 ), T‐cell restricted intracellular antigen 1 ( TIA1 ), and optineurin ( OPTN ), all of which share disruption of RNA stress granule function and autophagic degradation. This review will discuss each of the genes implicated in MSP, exploring the molecular pathogenesis, clinical features, current standards of care, and future directions for this diverse yet mechanistically linked spectrum of disorders.