RT Journal Article
SR Electronic
T1 Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 483
OP 489
DO 10.1136/jnnp-2014-309009
VO 86
IS 5
A1 Akinori Uruha
A1 Yukiko K Hayashi
A1 Yasushi Oya
A1 Madoka Mori-Yoshimura
A1 Masahiro Kanai
A1 Miho Murata
A1 Mayumi Kawamura
A1 Katsuhisa Ogata
A1 Tsuyoshi Matsumura
A1 Shigeaki Suzuki
A1 Yukako Takahashi
A1 Takayuki Kondo
A1 Takeshi Kawarabayashi
A1 Yuko Ishii
A1 Norito Kokubun
A1 Satoshi Yokoi
A1 Rei Yasuda
A1 Jun-ichi Kira
A1 Satomi Mitsuhashi
A1 Satoru Noguchi
A1 Ikuya Nonaka
A1 Ichizo Nishino
YR 2015
UL http://jnnp.bmj.com/content/86/5/483.abstract
AB 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.