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Neuromuscular
Research paper
Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure
  1. Akinori Uruha1,2,3,
  2. Yukiko K Hayashi1,2,4,
  3. Yasushi Oya5,
  4. Madoka Mori-Yoshimura5,
  5. Masahiro Kanai5,
  6. Miho Murata5,
  7. Mayumi Kawamura6,
  8. Katsuhisa Ogata7,
  9. Tsuyoshi Matsumura8,
  10. Shigeaki Suzuki9,
  11. Yukako Takahashi10,11,
  12. Takayuki Kondo11,
  13. Takeshi Kawarabayashi12,
  14. Yuko Ishii13,
  15. Norito Kokubun13,
  16. Satoshi Yokoi14,
  17. Rei Yasuda15,
  18. Jun-ichi Kira16,
  19. Satomi Mitsuhashi1,2,
  20. Satoru Noguchi1,2,
  21. Ikuya Nonaka2,7,
  22. Ichizo Nishino1,2
  1. 1Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan
  2. 2Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, Tokyo, Japan
  3. 3Department of Education, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan
  4. 4Department of Neurophysiology, Tokyo Medical University, Tokyo, Japan
  5. 5Department of Neurology, National Center Hospital, NCNP, Tokyo, Japan
  6. 6Department of Neurology, Japanese Red Cross Society, Wakayama Medical Center, Wakayama, Japan
  7. 7Institute of Clinical Research/Department of Neurology, National Hospital Organization Higashisaitama Hospital, Saitama, Japan
  8. 8Department of Neurology, National Hospital Organization Toneyama National Hospital, Osaka, Japan
  9. 9Department of Neurology, Keio University School of Medicine, Tokyo, Japan
  10. 10Department of Neurology, Osaka Red Cross Hospital, Osaka, Japan
  11. 11Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  12. 12Department of Neurology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Aomori, Japan
  13. 13Department of Neurology, Dokkyo Medical University, Tochigi, Japan
  14. 14Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  15. 15Department of Neurology, National Hospital Organization Maizuru Medical Center, Kyoto, Japan
  16. 16Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  1. Correspondence to Dr Ichizo Nishino, Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; nishino{at}ncnp.go.jp

Abstract

Background In hereditary myopathy with early respiratory failure (HMERF), cytoplasmic bodies (CBs) are often localised in subsarcolemmal regions, with necklace-like alignment (necklace CBs), in muscle fibres although their sensitivity and specificity are unknown.

Objective To elucidate the diagnostic value of the necklace CBs in the pathological diagnosis of HMERF among myofibrillar myopathies (MFMs).

Methods We sequenced the exon 343 of TTN gene (based on ENST00000589042), which encodes the fibronectin-3 (FN3) 119 domain of the A-band and is a mutational hot spot for HMERF, in genomic DNA from 187 patients from 175 unrelated families who were pathologically diagnosed as MFM. We assessed the sensitivity and specificity of the necklace CBs for HMERF by re-evaluating the muscle pathology of our patients with MFM.

Results TTN mutations were identified in 17 patients from 14 families, whose phenotypes were consistent with HMERF. Among them, 14 patients had necklace CBs. In contrast, none of other patients with MFM had necklace CBs except for one patient with reducing body myopathy. The sensitivity and specificity were 82% and 99%, respectively. Positive predictive value was 93% in the MFM cohort.

Conclusions The necklace CB is a useful diagnostic marker for HMERF. When muscle pathology shows necklace CBs, sequencing the FN3 119 domain of A-band in TTN should be considered.

  • MYOPATHY
  • PATHOLOGY

https://doi.org/10.1136/jnnp-2014-309009

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