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 Furuya & 41 others Shuntaro 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

37 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

Fingerprint

Genetic Association Studies
Hearing Loss
Cohort Studies
Mutation
Goiter
Vertigo
Genetic Counseling
Genetic Testing
Hearing
Genes
Genotype
Databases
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)

Cite this

Mutation spectrum and genotype-phenotype correlation of hearing loss patients caused by SLC26A4 mutations in the Japanese : A large cohort study. / Miyagawa, Maiko; Nishio, Shin Ya; Usami, Shin Ichi; Takeichi, Norihito; Fukuda, Satoshi; Namba, Atsushi; Shinkawa, Hideichi; Kobayashi, Yumiko; Sato, Hiroaki; Kawase, Tetsuaki; Kobayashi, Toshimitsu; Watanabe, Tomoo; Ito, Tsukasa; Aoyagi, Masaru; Ogawa, Hiroshi; Omori, Koichi; Ishikawa, Kotaro; Ichimura, Keiichi; Nagai, Kyoko; Furuya, Nobuhiko; Shigihara, Shuntaro; Nomura, Yasuyuki; Ikeda, Minoru; Ikezono, Tetsuo; Yagi, Toshiaki; Tomiyama, Shunichi; Kojima, Hiromi; Sakurai, Yuika; Moriyama, Hiroshi; Kumakawa, Kozo; Sano, Hajime; Okamoto, Makito; Iwasaki, Satoshi; Takeuchi, Kazuhiko; Nakai, Masako; Higashikawa, Masahiko; Takenaka, Hiroshi; Saito, Yuko; Sakagami, Masafumi; Naito, Yasushi; Fujihara, Keiji; Sakai, Akihiro; Yamanaka, Noboru; Fukushima, Kunihiro; Nishizaki, Kazunori; Sugahara, Kazuma; Yamashita, Hiroshi; Hato, Naoto; Gyo, Kiyofumi; Kakazu, Yasuhiro; Komune, Shizuo; Sugamura, Mayumi; Nakagawa, Takashi; Takahashi, Haruo; Kanda, Yukihiko; Kawano, Hirokazu; Tono, Tetsuya; Miyanohara, Ikuyo; Kurono, Yuichi; Ganaha, Akira; Suzuki, Mikio.

In: Journal of Human Genetics, Vol. 59, No. 5, 2014, p. 262-268.

Research output: Contribution to journalArticle

Miyagawa, M, Nishio, SY, Usami, SI, 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, Furuya, N, Shigihara, S, Nomura, Y, Ikeda, M, Ikezono, T, Yagi, T, Tomiyama, S, Kojima, H, Sakurai, Y, Moriyama, H, Kumakawa, K, Sano, H, Okamoto, M, Iwasaki, S, Takeuchi, K, Nakai, M, Higashikawa, M, Takenaka, H, Saito, Y, Sakagami, M, Naito, Y, Fujihara, K, Sakai, A, Yamanaka, N, Fukushima, K, Nishizaki, K, Sugahara, K, Yamashita, H, Hato, N, Gyo, K, Kakazu, Y, Komune, S, Sugamura, M, Nakagawa, T, Takahashi, H, Kanda, Y, Kawano, H, Tono, T, Miyanohara, I, Kurono, Y, Ganaha, A & 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, vol. 59, no. 5, pp. 262-268. https://doi.org/10.1038/jhg.2014.12
Miyagawa, Maiko ; Nishio, Shin Ya ; Usami, Shin Ichi ; Takeichi, Norihito ; Fukuda, Satoshi ; Namba, Atsushi ; Shinkawa, Hideichi ; Kobayashi, Yumiko ; Sato, Hiroaki ; Kawase, Tetsuaki ; Kobayashi, Toshimitsu ; Watanabe, Tomoo ; Ito, Tsukasa ; Aoyagi, Masaru ; Ogawa, Hiroshi ; Omori, Koichi ; Ishikawa, Kotaro ; Ichimura, Keiichi ; Nagai, Kyoko ; Furuya, Nobuhiko ; Shigihara, Shuntaro ; Nomura, Yasuyuki ; Ikeda, Minoru ; Ikezono, Tetsuo ; Yagi, Toshiaki ; Tomiyama, Shunichi ; Kojima, Hiromi ; Sakurai, Yuika ; Moriyama, Hiroshi ; Kumakawa, Kozo ; Sano, Hajime ; Okamoto, Makito ; Iwasaki, Satoshi ; Takeuchi, Kazuhiko ; Nakai, Masako ; Higashikawa, Masahiko ; Takenaka, Hiroshi ; Saito, Yuko ; Sakagami, Masafumi ; Naito, Yasushi ; Fujihara, Keiji ; Sakai, Akihiro ; Yamanaka, Noboru ; Fukushima, Kunihiro ; Nishizaki, Kazunori ; Sugahara, Kazuma ; Yamashita, Hiroshi ; Hato, Naoto ; Gyo, Kiyofumi ; Kakazu, Yasuhiro ; Komune, Shizuo ; Sugamura, Mayumi ; Nakagawa, Takashi ; Takahashi, Haruo ; Kanda, Yukihiko ; Kawano, Hirokazu ; Tono, Tetsuya ; Miyanohara, Ikuyo ; Kurono, Yuichi ; Ganaha, Akira ; Suzuki, Mikio. / Mutation spectrum and genotype-phenotype correlation of hearing loss patients caused by SLC26A4 mutations in the Japanese : A large cohort study. In: Journal of Human Genetics. 2014 ; Vol. 59, No. 5. pp. 262-268.
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AU - Miyagawa, Maiko

AU - Nishio, Shin Ya

AU - Usami, Shin Ichi

AU - Takeichi, Norihito

AU - Fukuda, Satoshi

AU - Namba, Atsushi

AU - Shinkawa, Hideichi

AU - Kobayashi, Yumiko

AU - Sato, Hiroaki

AU - Kawase, Tetsuaki

AU - Kobayashi, Toshimitsu

AU - Watanabe, Tomoo

AU - Ito, Tsukasa

AU - Aoyagi, Masaru

AU - Ogawa, Hiroshi

AU - Omori, Koichi

AU - Ishikawa, Kotaro

AU - Ichimura, Keiichi

AU - Nagai, Kyoko

AU - Furuya, Nobuhiko

AU - Shigihara, Shuntaro

AU - Nomura, Yasuyuki

AU - Ikeda, Minoru

AU - Ikezono, Tetsuo

AU - Yagi, Toshiaki

AU - Tomiyama, Shunichi

AU - Kojima, Hiromi

AU - Sakurai, Yuika

AU - Moriyama, Hiroshi

AU - Kumakawa, Kozo

AU - Sano, Hajime

AU - Okamoto, Makito

AU - Iwasaki, Satoshi

AU - Takeuchi, Kazuhiko

AU - Nakai, Masako

AU - Higashikawa, Masahiko

AU - Takenaka, Hiroshi

AU - Saito, Yuko

AU - Sakagami, Masafumi

AU - Naito, Yasushi

AU - Fujihara, Keiji

AU - Sakai, Akihiro

AU - Yamanaka, Noboru

AU - Fukushima, Kunihiro

AU - Nishizaki, Kazunori

AU - Sugahara, Kazuma

AU - Yamashita, Hiroshi

AU - Hato, Naoto

AU - Gyo, Kiyofumi

AU - Kakazu, Yasuhiro

AU - Komune, Shizuo

AU - Sugamura, Mayumi

AU - Nakagawa, Takashi

AU - Takahashi, Haruo

AU - Kanda, Yukihiko

AU - Kawano, Hirokazu

AU - Tono, Tetsuya

AU - Miyanohara, Ikuyo

AU - Kurono, Yuichi

AU - Ganaha, Akira

AU - Suzuki, Mikio

PY - 2014

Y1 - 2014

N2 - 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.

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KW - Congenital hearing loss

KW - DFNB4

KW - enlarged vestibular aqueduct

KW - goiter

KW - Pendred syndrome

KW - SLC26A4

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