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

Research output: Contribution to journalArticlepeer-review

133 Citations (Scopus)

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 - 1998

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Mutation in PEX16 is causal in the peroxisome-deficient Zellweger syndrome of complementation group D'. Together they form a unique fingerprint.

Cite this