Mutation spectrum and genotype-phenotype correlation of hearing loss patients caused by SLC26A4 mutations in the Japanese: A large cohort study

Maiko Miyagawa, 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

45 Citations (Scopus)

Abstract

Mutations in SLC26A4 cause a broad phenotypic spectrum, from typical Pendred syndrome to nonsyndromic hearing loss associated with enlarged vestibular aqueduct. Identification of these mutations is important for accurate diagnosis, proper medical management and appropriate genetic counseling and requires updated information regarding spectrum, clinical characteristics and genotype-phenotype correlations, based on a large cohort. In 100 patients with bilateral enlarged vestibular aqueduct among 1511 Japanese hearing loss probands registered in our gene bank, goiter data were available for 79, of whom 15 had Pendred syndrome and 64 had nonsyndromic hearing loss. We clarified the mutation spectrum for the SLC26A4 mutations and also summarized hearing levels, progression, fluctuation and existence of genotype-phenotype correlation. SLC26A4 mutations were identified in 82 of the 100 patients (82.0%). Of the Pendred syndrome patients, 93% (14/15) were carriers, as were 77% (49/64) of the nonsyndromic hearing loss patients. Clinical characteristics of patients with SLC26A4 mutations were congenital, fluctuating and progressive hearing loss usually associated with vertigo and/or goiter. We found no genotype-phenotype correlations, indicating that, unlike in the case of GJB2 mutations, the phenotype cannot be predicted from the genotype. Our mutation analysis confirmed the importance of mutations in the SLC26A4 gene among hearing loss patients with enlarged vestibular aqueduct and revealed the mutation spectrum, essential information when performing genetic testing.

Original languageEnglish
Pages (from-to)262-268
Number of pages7
JournalJournal of Human Genetics
Volume59
Issue number5
DOIs
Publication statusPublished - 2014 May

Keywords

  • Congenital hearing loss
  • DFNB4
  • Pendred syndrome
  • SLC26A4
  • enlarged vestibular aqueduct
  • goiter

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Miyagawa, M., 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). Mutation spectrum and genotype-phenotype correlation of hearing loss patients caused by SLC26A4 mutations in the Japanese: A large cohort study. Journal of Human Genetics, 59(5), 262-268. https://doi.org/10.1038/jhg.2014.12