Exome sequencing identifies a novel TTN mutation in a family with hereditary myopathy with early respiratory failure

Rumiko Izumi, Tetsuya Niihori, Yoko Aoki, Naoki Suzuki, Masaaki Kato, Hitoshi Warita, Toshiaki Takahashi, Maki Tateyama, Takeshi Nagashima, Ryo Funayama, Koji Abe, Keiko Nakayama, Masashi Aoki, Yoichi Matsubara

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Myofibrillar myopathy (MFM) is a group of chronic muscular disorders that show the focal dissolution of myofibrils and accumulation of degradation products. The major genetic basis of MFMs is unknown. In 1993, our group reported a Japanese family with dominantly inherited cytoplasmic body myopathy, which is now included in MFM, characterized by late-onset chronic progressive distal muscle weakness and early respiratory failure. In this study, we performed linkage analysis and exome sequencing on these patients and identified a novel c.90263G>T mutation in the TTN gene (NM-001256850). During the course of our study, another groups reported three mutations in TTN in patients with hereditary myopathy with early respiratory failure (HMERF, MIM #603689), which is characterized by overlapping pathologic findings with MFMs. Our patients were clinically compatible with HMERF. The mutation identified in this study and the three mutations in patients with HMERF were located on the A-band domain of titin, suggesting a strong relationship between mutations in the A-band domain of titin and HMERF. Mutation screening of TTN has been rarely carried out because of its huge size, consisting of 363 exons. It is possible that focused analysis of TTN may detect more mutations in patients with MFMs, especially in those with early respiratory failure.

Original languageEnglish
Pages (from-to)259-266
Number of pages8
JournalJournal of Human Genetics
Volume58
Issue number5
DOIs
Publication statusPublished - May 1 2013

Keywords

  • A-band
  • Fn3 domain
  • HMERF
  • TTN
  • cytoplasmic body
  • hereditary myopathy with early respiratory failure
  • myofibrillar myopathy
  • titin

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Izumi, R., Niihori, T., Aoki, Y., Suzuki, N., Kato, M., Warita, H., Takahashi, T., Tateyama, M., Nagashima, T., Funayama, R., Abe, K., Nakayama, K., Aoki, M., & Matsubara, Y. (2013). Exome sequencing identifies a novel TTN mutation in a family with hereditary myopathy with early respiratory failure. Journal of Human Genetics, 58(5), 259-266. https://doi.org/10.1038/jhg.2013.9