Rhizomelic chondrodysplasia punctata is caused by deficiency of human pex7, a homologue of the yeast pts2 receptor

ABSTRACT The rhizomelic form of chondrodysplasia punctata (RCDP) is an autosomal recessive disease of peroxisome biogenesis characterized by deficiencies in several peroxisomal proteins,

including the peroxisomal enzymes of plasmalogen biosynthesis and peroxisomal 3-ketoacyl thiolase1. In cultured fibroblasts from patients with this disorder, both the peroxisomal targeting

and proteolytic removal of the amino-terminal type 2 peroxisomal targeting sequence (PTS2) of thiolase are defective, whereas the biogenesis of proteins targeted by car boxy-terminal type 1

peroxisomal targeting sequences (PTS1) is unimpaired. We have previously isolated a _Saccharomyces cerevisiae_ peroxisomal biogenesis mutant, _pex7_ (formerly _peb1/pas7_)2, which

demonstrates a striking similarity to the cellular phenotype of RCDP fibroblasts in that PTS1 targeting is functional, but the peroxisomal packaging of PTS2 targeted thiolase is lacking.

Complementation of this mutant has led to the identification of the protein ScPex7p3,4, a PTS2 receptor5,6. In this paper we report cloning of the human orthologue of Sc_PEX7_, and

demonstrate that this is the defective gene in RCDP. We show that expression of human PEX7 in RCDP cells rescues PTS2 targeting and restores some activity of dihydroxyacetone phosphate

acyltransferase (DHAP-AT), a peroxisomal enzyme of plasmalogen biosynthesis, and we identify the mutations responsible for loss of function of PEX7 in a compound heterozygote RCDP patient.

These results imply that several peroxisomal proteins are targeted by PTS2 signals and that the various biochemical and clinical defects in RCDP result from a defect in the receptor for this

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destruction in vivo. _J. Biol. Chem._ 237, 3468–3475 (1962). PubMed  CAS  Google Scholar  Download references AUTHOR INFORMATION Author notes * P. Edward Purdue and Jing Wei Zhang: P.E.R

& J.W.Z. both made major contributions to this work. AUTHORS AND AFFILIATIONS * Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, 1190 Fifth Avenue - , Box 1007,

New York, NY, 10029-6574 Marek Skoneczny & Paul B. Lazarow Authors * P. Edward Purdue View author publications You can also search for this author inPubMed Google Scholar * Jing Wei

Zhang View author publications You can also search for this author inPubMed Google Scholar * Marek Skoneczny View author publications You can also search for this author inPubMed Google

Scholar * Paul B. Lazarow View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Paul B. Lazarow. RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Purdue, P., Zhang, J., Skoneczny, M. _et al._ Rhizomelic chondrodysplasia punctata is caused by deficiency of human PEX7, a

homologue of the yeast PTS2 receptor. _Nat Genet_ 15, 381–384 (1997). https://doi.org/10.1038/ng0497-381 Download citation * Received: 30 December 1996 * Accepted: 05 February 1997 * Issue

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