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Review
. 2021 Apr;63(4):442-454.
doi: 10.1002/mus.27097. Epub 2020 Nov 3.

Multisystem proteinopathy: Where myopathy and motor neuron disease converge

Manisha K Korb  1 , Virginia E Kimonis  2 , Tahseen Mozaffar  1   3   4
Affiliations
Free article
Review

Multisystem proteinopathy: Where myopathy and motor neuron disease converge

Manisha K Korb et al. Muscle Nerve. 2021 Apr.
Free article

Abstract

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.

Keywords: Paget disease of bone; VCP; amyotrophic lateral sclerosis; inclusion body myopathy; multiple system proteinopathy.

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References

REFERENCE

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