Mutation in PEX16 is causal in the peroxisome-deficient Zellweger syndrome of complementation group D

Masanori Honsho, Shigehiko Tamura, Nobuyuki Shimozawa, Yasuyuki Suzuki, Naomi Kondo, Yukio Fujiki

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Abstract

Peroxisome-biogenesis disorders (PBDs), including Zellweger syndrome (ZS), are autosomal recessive diseases caused by a deficiency in peroxisome assembly as well as by a malfunction of peroxisomes, among which >10 genotypes have been identified. We have isolated a human PEX16 cDNA (HsPEX16) by performing an expressed-sequence-tag homology search on a human DNA database, by using yeast PEX16 from Yarrowia lipolytica and then screening the human liver cDNA library. This cDNA encodes a peroxisomal protein (a peroxin Pex16p) made up of 336 amino acids. Among 13 peroxisome-deficiency complementation groups (CGs), HsPEX16 expression morphologically and biochemically restored peroxisome biogenesis only in fibroblasts from a CG-D patient with ZS in Japan (the same group as CG-IX in the United States). Pex16p was localized to peroxisomes through expression study of epitope- tagged Pex16p. One patient (PBDD-01) possessed a homozygous, inactivating nonsense mutation, C→T at position 526 in a codon (CGA) for 176 Arg, that resulted in a termination codon (TGA). This implies that the C-terminal half is required for the biological function of Pex16p. PBDD-01-derived PEX16 cDNA was defective in peroxisome-restoring activity when expressed in the patient's fibroblasts. These results demonstrate that mutation in PEX16 is the genetic cause of CG-D PBDs.

Original languageEnglish
Pages (from-to)1622-1630
Number of pages9
JournalAmerican journal of human genetics
Volume63
Issue number6
DOIs
Publication statusPublished - Jan 1 1998

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Zellweger Syndrome
Peroxisomes
Mutation
Complementary DNA
Fibroblasts
Yarrowia
Terminator Codon
Nonsense Codon
Expressed Sequence Tags
Nucleic Acid Databases
Sequence Homology
Gene Library
Codon
Epitopes
Japan
Yeasts
Genotype
Amino Acids
Liver

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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Mutation in PEX16 is causal in the peroxisome-deficient Zellweger syndrome of complementation group D. / Honsho, Masanori; Tamura, Shigehiko; Shimozawa, Nobuyuki; Suzuki, Yasuyuki; Kondo, Naomi; Fujiki, Yukio.

In: American journal of human genetics, Vol. 63, No. 6, 01.01.1998, p. 1622-1630.

Research output: Contribution to journalArticle

Honsho, Masanori ; Tamura, Shigehiko ; Shimozawa, Nobuyuki ; Suzuki, Yasuyuki ; Kondo, Naomi ; Fujiki, Yukio. / Mutation in PEX16 is causal in the peroxisome-deficient Zellweger syndrome of complementation group D. In: American journal of human genetics. 1998 ; Vol. 63, No. 6. pp. 1622-1630.
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