title: Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata.
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.
authors.affiliation: Department of Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: N
authors.initials: N
authors.lastname: Braverman
authors.forename: G
authors.initials: G
authors.lastname: Steel
authors.forename: C
authors.initials: C
authors.lastname: Obie
authors.forename: A
authors.initials: A
authors.lastname: Moser
authors.forename: H
authors.initials: H
authors.lastname: Moser
authors.forename: S J
authors.initials: SJ
authors.lastname: Gould
authors.forename: D
authors.initials: D
authors.lastname: Valle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D018902:Chondrodysplasia Punctata, Rhizomelic / Q000235:genetics*; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity; D000074437:Peroxisomal Targeting Signal 2 Receptor; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; C000614269:PEX7 protein, human; D000074437:Peroxisomal Targeting Signal 2 Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins