, Volume 15, Issue 3, pp 151–156 | Cite as

Novel recessive myotilin mutation causes severe myofibrillar myopathy

  • Joachim Schessl
  • Elisa Bach
  • Simone Rost
  • Sarah Feldkirchner
  • Christiana Kubny
  • Stefan Müller
  • Franz-Georg Hanisch
  • Wolfram Kress
  • Benedikt Schoser
Short Communication


We identified the first homozygous and hence recessive mutation in the myotilin gene (MYOT) in a family affected by a severe myofibrillar myopathy (MFM). MFM is a rare, progressive and devastating disease of human skeletal muscle with distinct histopathological pattern of protein aggregates and myofibrillar degeneration. So far, only heterozygous missense mutations in MYOT have been associated with autosomal dominant myofibrillar myopathy, limb-girdle muscular dystrophy type 1A and distal myopathy. Myotilin itself is highly expressed in skeletal and cardiac muscle and is localized at the Z-disc and therefore interacts in sarcomere assembly. We performed whole-exome sequencing in a German family clinically diagnosed with MFM and identified a homozygous mutation in exon 2, c.16C > G (p.Arg6Gly). Using laser microdissection followed by quantitative mass spectrometry, we identified the myotilin protein as one component showing the highest increased abundance in the aggregates in the index patient. We suggest that the combined approach has a high potential as a new tool for the confirmation of unclassified variants which are found in whole-exome sequencing approaches.


Myotilin Myofibrillar myopathy Recessive muscle disease Whole-exome sequencing 



We would like to thank the patients reported here for their participation and encouragement. We thank Ursula Klutzny and Maria Schmuck for the technical assistance. We also would like to thank Dr. Michael A. Hauser (Duke University Medical Center, Durham, NC, USA) for the myotilin antibody. J.S., F.G.H., W.K. and B.S. are supported by the German Research Association (DFG, FOR1228) and are members of the German network on muscular dystrophies (MD-NET funded by BMBF, Bonn, Germany; MD-NET is a partner of TREAT-NMD (EC, 6th FP, proposal no. 036825;


The authors have reported no conflicts of interest.

Supplementary material

10048_2014_410_MOESM1_ESM.doc (39 kb)
ESM 1 (DOC 39 kb)
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Suppl. Table 1 (DOC 38 kb)
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Suppl. Figure 1

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Joachim Schessl
    • 1
  • Elisa Bach
    • 2
  • Simone Rost
    • 2
  • Sarah Feldkirchner
    • 1
  • Christiana Kubny
    • 1
  • Stefan Müller
    • 3
  • Franz-Georg Hanisch
    • 3
  • Wolfram Kress
    • 2
  • Benedikt Schoser
    • 1
  1. 1.Friedrich-Baur-Institute, Department of NeurologyLudwig-Maximilians University of MunichMunichGermany
  2. 2.Department of Human GeneticsJulius-Maximilian UniversityWürzburgGermany
  3. 3.Central Bioanalytics, Center for Molecular Medicine CologneUniversity of CologneKölnGermany

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