Mutations in PEX10 is the cause of Zellweger peroxisome deficiency syndrome of complementation group B

Kanji Okumoto, Ryota Itoh, Nobuyuki Shimozawa, Yasuyuki Suzuki, Shigehiko Tamura, Naomi Kondo, Yukio Fujiki

研究成果: ジャーナルへの寄稿記事

87 引用 (Scopus)

抄録

Peroxisome biogenesis disorders (PBD), such as Zellweger syndrome, are autosomal recessive diseases caused by a deficiency in peroxisome assembly as well as a malfunction of the peroxisomes, where at least 10 genotypes have been reported. We have isolated a human PEX10 cDNA (HsPEX10) by an expressed sequence tag homology search on a human DNA database using yeast PEX10 from Hansenula polymorpha, followed by screening of a human liver cDNA library. This cDNA encodes a peroxisomal protein (a peroxin Pex10p) comprising 326 amino acids, with two putative transmembrane segments and a C3HC4 zinc finger RING motif. Both the N- and C-terminal regions of Pex10p are exposed to the cytosol, as assessed by an expression study of epitope-tagged Pex10p. HsPEX10 expression morphologically and biochemically restored peroxisome biogenesis in fibroblasts from Zellweger patients of complementation group B in Japan (complementation group VII in the USA). One patient (PBDB-01) possessed a homozygous, inactivating mutation, a 2 bp deletion immediately upstream of the RING motif, which resulted in a frameshift, altering 65 amino acids from the normal. This implies that the C-terminal part, including the RING finger, is required for biological function of Pex10p. PEX10 cDNA derived from patient PBDB-01 was defective in peroxisome-restoring activity when expressed in patient fibroblasts. These results demonstrate that mutation in PEX10 is the genetic cause of complementation group B PBD.

元の言語英語
ページ(範囲)1399-1405
ページ数7
ジャーナルHuman Molecular Genetics
7
発行部数9
DOI
出版物ステータス出版済み - 9 1 1998

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Peroxisomes
Mutation
Complementary DNA
Fibroblasts
Zellweger Syndrome
Amino Acids
Pichia
Expressed Sequence Tags
Zinc Fingers
Nucleic Acid Databases
Sequence Homology
Gene Library
Cytosol
Epitopes
Japan
Yeasts
Genotype
Liver
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

これを引用

Mutations in PEX10 is the cause of Zellweger peroxisome deficiency syndrome of complementation group B. / Okumoto, Kanji; Itoh, Ryota; Shimozawa, Nobuyuki; Suzuki, Yasuyuki; Tamura, Shigehiko; Kondo, Naomi; Fujiki, Yukio.

:: Human Molecular Genetics, 巻 7, 番号 9, 01.09.1998, p. 1399-1405.

研究成果: ジャーナルへの寄稿記事

Okumoto, Kanji ; Itoh, Ryota ; Shimozawa, Nobuyuki ; Suzuki, Yasuyuki ; Tamura, Shigehiko ; Kondo, Naomi ; Fujiki, Yukio. / Mutations in PEX10 is the cause of Zellweger peroxisome deficiency syndrome of complementation group B. :: Human Molecular Genetics. 1998 ; 巻 7, 番号 9. pp. 1399-1405.
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