• 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 Noguchi, Ikuya Nonaka, and Ichizo Nishino.
• Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, Tokyo, Japan Department of Education, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
• J. Neurol. Neurosurg. Psychiatr.. 2015 May 1;86(5):483-9.

BackgroundIn 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.ObjectiveTo elucidate the diagnostic value of the necklace CBs in the pathological diagnosis of HMERF among myofibrillar myopathies (MFMs).MethodsWe 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.ResultsTTN 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.ConclusionsThe 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.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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