Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure

Akinori Uruha, Yukiko K. Hayashi, Yasushi Oya, Madoka Mori-Yoshimura, Masahiro Kanai, Miho Murata, Mayumi Kawamura, Katsuhisa Ogata, Tsuyoshi Matsumura, Shigeaki Suzuki, Yukako Takahashi, Takayuki Kondo, Takeshi Kawarabayashi, Yuko Ishii, Norito Kokubun, Satoshi Yokoi, Rei Yasuda, Jun Ichi Kira, Satomi Mitsuhashi, Satoru NoguchiIkuya Nonaka, Ichizo Nishino

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13 Citations (Scopus)

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 speci ficity 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.

Original languageEnglish
Pages (from-to)483-489
Number of pages7
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume86
Issue number5
DOIs
Publication statusPublished - May 1 2015

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All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Uruha, A., Hayashi, Y. K., Oya, Y., Mori-Yoshimura, M., Kanai, M., Murata, M., ... Nishino, I. (2015). Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure. Journal of Neurology, Neurosurgery and Psychiatry, 86(5), 483-489. https://doi.org/10.1136/jnnp-2014-309009