Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure

作者：Uruha Akinori; Hayashi Yukiko K; Oya Yasushi; Mori Yoshimura Madoka; Kanai Masahiro; Murata Miho; Kawamura Mayumi; Ogata Katsuhisa; Matsumura Tsuyoshi; Suzuki Shigeaki; Takahashi Yukako; Kondo Takayuki; Kawarabayashi Takeshi; Ishii Yuko; Kokubun Norito; Yokoi Satoshi; Yasuda Rei; Kira Jun ichi; Mitsuhashi Satomi; Noguchi Satoru; Nonaka Ikuya; Nishino Ichizo^*

来源：Journal of Neurology Neurosurgery and Psychiatry, 2015, 86(5): 483-489.

DOI：10.1136/jnnp-2014-309009

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.

• 出版日期2015-5