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Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata

Nature Geneticsvolume 15pages369376 (1997) | Download Citation

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Abstract

Rhizomelic chondrodysplasia punctata (RCDP) is a rare autosomal recessive phenotype that comprises complementation group 11 of the peroxisome biogenesis disorders (PBD). PEX7, a candidate gene for RCDP identified in yeast, encodes the receptor for peroxisomal matrix proteins with the type-2 peroxisome targeting signal (PTS2). By homology probing we identified human and murine PEX7 genes and found that expression of either corrects the PTS2-import defect characteristic of RCDP cells. In a collection of 36 RCDP probands, we found two inactivating PEX7 mutations: one, L292ter, was present in 26 of the probands, all with a severe phenotype; the second, A218V, was present in three probands, including two with a milder phenotype. A third mutation, G217R, whose functional significance is yet to be determined, was present in five probands, all compound heterozygotes with L292ter. We conclude that PEX7 is responsible for RCDP (PBD CG11) and suggest a founder effect may explain the high frequency of L292ter.

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Affiliations

  1. Department of Pediatrics, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland, 21205, USA

    • Nancy Braverman
    • , Gary Steel
    •  & David Valle
  2. Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland, 21205, USA

    • Cassandra Obie
    •  & David Valle
  3. Kennedy Krieger Institute, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland, 21205, USA

    • Ann Moser
    •  & Hugo Moser
  4. Department of Cell Biology and Anatomy, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland, 21205, USA

    • Stephen J. Gould

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Correspondence to David Valle.

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https://doi.org/10.1038/ng0497-369

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