Novel mutations of the GLA gene in Japanese patients with Fabry disease and their functional characterization by active site specific chaperone.

Masaaki Shimotori, Hiroki Maruyama, Gen Nakamura, Takayuki Suyama, Fumiko Sakamoto, Masaaki Itoh, Shigeaki Miyabayashi, Takahiro Ohnishi, Norio Sakai, Mari Wataya-Kaneda, Mitsuru Kubota, Toshiyuki Takahashi, Tatsuhiko Mori, Katsuhiko Tamura, Shinji Kageyama, Nobuo Shio, Teruhiko Maeba, Hirokazu Yahagi, Motoko Tanaka, Masayo OkaHitoshi Sugiyama, Toshiyuki Sugawara, Noriko Mori, Hiroko Tsukamoto, Keiichi Tamagaki, Shuuji Tanda, Yuka Suzuki, Chiya Shinonaga, Jun ichi Miyazaki, Satoshi Ishii, Fumitake Gejyo

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Fabry disease is an X-linked recessive inborn metabolic disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (EC 3.2.1.22). The causative mutations are diverse, include both large rearrangements and single-base substitutions, and are dispersed throughout the 7 exons of the alpha-galactosidase A gene (GLA). Mutation hotspots for Fabry disease do not exist. We examined 62 Fabry patients in Japan and found 24 GLA mutations, including 11 novel ones. A potential treatment reported for Fabry disease is active site specific chaperone (ASSC) therapy using 1-deoxygalactonojirimycin (DGJ), an inhibitor of alpha-galactosidase A, at subinhibitory concentrations. We transfected COS-7 cells with the 24 mutant GLAs and analyzed the alpha-galactosidase A activities. We then treated the transfected COS-7 cells with DGJ and analyzed its effect on the mutant enzyme activities. The activity of 11 missense mutants increased significantly with DGJ. Although ASSC therapy is useful only for misfolding mutants and therefore not applicable to all cases, it may be useful for treating many Japanese patients with Fabry disease. (c) 2007 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)331
Number of pages1
JournalHuman Mutation
Volume29
Issue number2
Publication statusPublished - Feb 2008
Externally publishedYes

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Galactosidases
alpha-Galactosidase
Fabry Disease
Catalytic Domain
Mutation
COS Cells
Genes
Enzymes
Exons
Japan
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Shimotori, M., Maruyama, H., Nakamura, G., Suyama, T., Sakamoto, F., Itoh, M., ... Gejyo, F. (2008). Novel mutations of the GLA gene in Japanese patients with Fabry disease and their functional characterization by active site specific chaperone. Human Mutation, 29(2), 331.

Novel mutations of the GLA gene in Japanese patients with Fabry disease and their functional characterization by active site specific chaperone. / Shimotori, Masaaki; Maruyama, Hiroki; Nakamura, Gen; Suyama, Takayuki; Sakamoto, Fumiko; Itoh, Masaaki; Miyabayashi, Shigeaki; Ohnishi, Takahiro; Sakai, Norio; Wataya-Kaneda, Mari; Kubota, Mitsuru; Takahashi, Toshiyuki; Mori, Tatsuhiko; Tamura, Katsuhiko; Kageyama, Shinji; Shio, Nobuo; Maeba, Teruhiko; Yahagi, Hirokazu; Tanaka, Motoko; Oka, Masayo; Sugiyama, Hitoshi; Sugawara, Toshiyuki; Mori, Noriko; Tsukamoto, Hiroko; Tamagaki, Keiichi; Tanda, Shuuji; Suzuki, Yuka; Shinonaga, Chiya; Miyazaki, Jun ichi; Ishii, Satoshi; Gejyo, Fumitake.

In: Human Mutation, Vol. 29, No. 2, 02.2008, p. 331.

Research output: Contribution to journalArticle

Shimotori, M, Maruyama, H, Nakamura, G, Suyama, T, Sakamoto, F, Itoh, M, Miyabayashi, S, Ohnishi, T, Sakai, N, Wataya-Kaneda, M, Kubota, M, Takahashi, T, Mori, T, Tamura, K, Kageyama, S, Shio, N, Maeba, T, Yahagi, H, Tanaka, M, Oka, M, Sugiyama, H, Sugawara, T, Mori, N, Tsukamoto, H, Tamagaki, K, Tanda, S, Suzuki, Y, Shinonaga, C, Miyazaki, JI, Ishii, S & Gejyo, F 2008, 'Novel mutations of the GLA gene in Japanese patients with Fabry disease and their functional characterization by active site specific chaperone.', Human Mutation, vol. 29, no. 2, pp. 331.
Shimotori, Masaaki ; Maruyama, Hiroki ; Nakamura, Gen ; Suyama, Takayuki ; Sakamoto, Fumiko ; Itoh, Masaaki ; Miyabayashi, Shigeaki ; Ohnishi, Takahiro ; Sakai, Norio ; Wataya-Kaneda, Mari ; Kubota, Mitsuru ; Takahashi, Toshiyuki ; Mori, Tatsuhiko ; Tamura, Katsuhiko ; Kageyama, Shinji ; Shio, Nobuo ; Maeba, Teruhiko ; Yahagi, Hirokazu ; Tanaka, Motoko ; Oka, Masayo ; Sugiyama, Hitoshi ; Sugawara, Toshiyuki ; Mori, Noriko ; Tsukamoto, Hiroko ; Tamagaki, Keiichi ; Tanda, Shuuji ; Suzuki, Yuka ; Shinonaga, Chiya ; Miyazaki, Jun ichi ; Ishii, Satoshi ; Gejyo, Fumitake. / Novel mutations of the GLA gene in Japanese patients with Fabry disease and their functional characterization by active site specific chaperone. In: Human Mutation. 2008 ; Vol. 29, No. 2. pp. 331.
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