What causes sarcotubular myopathy?

Updated: Mar 11, 2019
  • Author: Matthew Harmelink, MD; Chief Editor: Amy Kao, MD  more...
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Answer

This myopathy is due to a mutation in Tripartite-motif containing gene 32 (TRIM32).

Inheritance is autosomal recessive, and all cases have the same mutation (D487N) that causes limb-girdle muscular dystrophy 2H (Manitoba Hutterite dystrophy).

TRIM 32 is an E3 ubiquitin ligase that is expressed in muscle. It interacts with myosin and can ubiquinate actin. E3 ubiquitin ligase activity is not abolished due to this mutation. Nevertheless, altered ability to ubiquinate may result in accumulation of proteins that are not tagged for degradation by the proteosomal system. [65]

EM reveals numerous small, membrane-bound vacuoles that appear to originate from the sarcotubular system and have reactivity to T-tubule and SR-associated proteins, most often affecting type-2 muscle fibers.

Inheritance is autosomal recessive. Onset occurs in childhood in most, but in mid-adult life in some, with mild-to-moderate proximal weakness and mild facial weakness. Other features include muscle atrophy, contractures, exercise-induced myalgias, and scapular winging. This disease is allelic with LGMD 2H (Limb-Girdle Muscular Dystrophy) making it likely that these two diseases are the same disorder. [66]


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