Frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening

Takuya Yano, Shin Ya Nishio, Shin Ichi Usami, Norihito Takeichi, Satoshi Fukuda, Atsushi Namba, Hideichi Shinkawa, Yumiko Kobayashi, Hiroaki Sato, Tetsuaki Kawase, Toshimitsu Kobayashi, Tomoo Watanabe, Tsukasa Ito, Masaru Aoyagi, Hiroshi Ogawa, Koichi Omori, Kotaro Ishikawa, Keiichi Ichimura, Kyoko Nagai, Nobuhiko FuruyaShuntaro Shigihara, Yasuyuki Nomura, Minoru Ikeda, Tetsuo Ikezono, Toshiaki Yagi, Shunichi Tomiyama, Hiromi Kojima, Yuika Sakurai, Hiroshi Moriyama, Kozo Kumakawa, Hajime Sano, Makito Okamoto, Satoshi Iwasaki, Kazuhiko Takeuchi, Masako Nakai, Masahiko Higashikawa, Hiroshi Takenaka, Yuko Saito, Masafumi Sakagami, Yasushi Naito, Keiji Fujihara, Akihiro Sakai, Noboru Yamanaka, Kunihiro Fukushima, Kazunori Nishizaki, Kazuma Sugahara, Hiroshi Yamashita, Naoto Hato, Kiyofumi Gyo, Yasuhiro Kakazu, Shizuo Komune, Mayumi Sugamura, Takashi Nakagawa, Haruo Takahashi, Yukihiko Kanda, Hirokazu Kawano, Tetsuya Tono, Ikuyo Miyanohara, Yuichi Kurono, Akira Ganaha, Mikio Suzuki

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Mutations in mitochondrial DNA (mtDNA) are reported to be responsible for the pathogenesis of maternally inherited hearing loss. Complete mtDNA sequencing may detect pathogenic mutations, but whether they are indeed pathogenic can be difficult to interpret because of normal ethnic-associated haplogroup variation and other rare variations existing among control populations. In this study, we performed systemic mutational analysis of mtDNA in 394 Japanese patients with hearing loss. Two different cohorts were analyzed in this study: Cohort 1, 254 maternally inherited patients; and Cohort 2, 140 patients with various inheritance modes. After screening of the entire mtDNA genome with direct sequencing, we evaluated the frequency of previously reported mutations and the frequency and pathogenicity of the novel variants. As a result, the 'Confirmed' mitochondrial mutations were found predominantly in Cohort 1 rather than in Cohort 2 (14.6 vs 0.7%). 1555A>G (n=23) is the most common mutation, followed by the 3243A>G (n=11) mutations. On the basis of prediction analysis, we detected 10 novel homoplasmic mitochondrial variants. After further classification, the 3595A>G and 6204A>G variants were found to be new candidate mutations possibly associated with hearing loss.

Original languageEnglish
Pages (from-to)100-106
Number of pages7
JournalJournal of Human Genetics
Volume59
Issue number2
DOIs
Publication statusPublished - Feb 1 2014

Keywords

  • Mitochondrial mutation
  • Non-syndromic hearing loss

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Yano, T., Nishio, S. Y., Usami, S. I., Takeichi, N., Fukuda, S., Namba, A., Shinkawa, H., Kobayashi, Y., Sato, H., Kawase, T., Kobayashi, T., Watanabe, T., Ito, T., Aoyagi, M., Ogawa, H., Omori, K., Ishikawa, K., Ichimura, K., Nagai, K., ... Suzuki, M. (2014). Frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening. Journal of Human Genetics, 59(2), 100-106. https://doi.org/10.1038/jhg.2013.128