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 Noguchi & 2 others Ikuya Nonaka, Ichizo Nishino

Research output: Contribution to journalArticle

11 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 - 2015 May 1

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Fibronectins
Muscles
Pathology
Sensitivity and Specificity
Muscular Diseases
Hereditary Myopathy with Early Respiratory Failure
Necklace
Exons
Myofibrillar Myopathy
Phenotype
Mutation
DNA
Genes
Specificity
Diagnostics

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery
  • Arts and Humanities (miscellaneous)
  • Medicine(all)

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

Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure. / 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.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 86, No. 5, 01.05.2015, p. 483-489.

Research output: Contribution to journalArticle

Uruha, A, Hayashi, YK, Oya, Y, Mori-Yoshimura, M, Kanai, M, Murata, M, Kawamura, M, Ogata, K, Matsumura, T, Suzuki, S, Takahashi, Y, Kondo, T, Kawarabayashi, T, Ishii, Y, Kokubun, N, Yokoi, S, Yasuda, R, Kira, JI, Mitsuhashi, S, Noguchi, S, Nonaka, I & Nishino, I 2015, 'Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure', Journal of Neurology, Neurosurgery and Psychiatry, vol. 86, no. 5, pp. 483-489. https://doi.org/10.1136/jnnp-2014-309009
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. / Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure. In: Journal of Neurology, Neurosurgery and Psychiatry. 2015 ; Vol. 86, No. 5. pp. 483-489.
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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.",
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T1 - Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure

AU - Uruha, Akinori

AU - Hayashi, Yukiko K.

AU - Oya, Yasushi

AU - Mori-Yoshimura, Madoka

AU - Kanai, Masahiro

AU - Murata, Miho

AU - Kawamura, Mayumi

AU - Ogata, Katsuhisa

AU - Matsumura, Tsuyoshi

AU - Suzuki, Shigeaki

AU - Takahashi, Yukako

AU - Kondo, Takayuki

AU - Kawarabayashi, Takeshi

AU - Ishii, Yuko

AU - Kokubun, Norito

AU - Yokoi, Satoshi

AU - Yasuda, Rei

AU - Kira, Jun Ichi

AU - Mitsuhashi, Satomi

AU - Noguchi, Satoru

AU - Nonaka, Ikuya

AU - Nishino, Ichizo

PY - 2015/5/1

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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 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.

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 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.

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