TY - JOUR T1 - Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure JF - Journal of Neurology, Neurosurgery & Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 483 LP - 489 DO - 10.1136/jnnp-2014-309009 VL - 86 IS - 5 AU - Akinori Uruha AU - Yukiko K Hayashi AU - Yasushi Oya AU - Madoka Mori-Yoshimura AU - Masahiro Kanai AU - Miho Murata AU - Mayumi Kawamura AU - Katsuhisa Ogata AU - Tsuyoshi Matsumura AU - Shigeaki Suzuki AU - Yukako Takahashi AU - Takayuki Kondo AU - Takeshi Kawarabayashi AU - Yuko Ishii AU - Norito Kokubun AU - Satoshi Yokoi AU - Rei Yasuda AU - Jun-ichi Kira AU - Satomi Mitsuhashi AU - Satoru Noguchi AU - Ikuya Nonaka AU - Ichizo Nishino Y1 - 2015/05/01 UR - http://jnnp.bmj.com/content/86/5/483.abstract N2 - 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. ER -