title: A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata (CDPX) and implications for warfarin embryopathy.
abstract: X-linked recessive chondrodysplasia punctata (CDPX) is a congenital defect of bone and cartilage development characterized by aberrant bone mineralization, severe underdevelopment of nasal cartilage, and distal phalangeal hypoplasia. A virtually identical phenotype is observed in the warfarin embryopathy, which is due to the teratogenic effects of coumarin derivatives during pregnancy. We have cloned the genomic region within Xp22.3 where the CDPX gene has been assigned and isolated three adjacent genes showing highly significant homology to the sulfatase gene family. Point mutations in one of these genes were identified in five patients with CDPX. Expression of this gene in COS cells resulted in a heat-labile arylsulfatase activity that is inhibited by warfarin. A deficiency of a heat-labile arylsulfatase activity was demonstrated in patients with deletions spanning the CDPX region. These data indicate that CDPX is caused by an inherited deficiency of a novel sulfatase and suggest that warfarin embryopathy might involve drug-induced inhibition of the same enzyme.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: B
authors.initials: B
authors.lastname: Franco
authors.forename: G
authors.initials: G
authors.lastname: Meroni
authors.forename: G
authors.initials: G
authors.lastname: Parenti
authors.forename: J
authors.initials: J
authors.lastname: Levilliers
authors.forename: L
authors.initials: L
authors.lastname: Bernard
authors.forename: M
authors.initials: M
authors.lastname: Gebbia
authors.forename: L
authors.initials: L
authors.lastname: Cox
authors.forename: P
authors.initials: P
authors.lastname: Maroteaux
authors.forename: L
authors.initials: L
authors.lastname: Sheffield
authors.forename: G A
authors.initials: GA
authors.lastname: Rappold
authors.forename: G
authors.initials: G
authors.lastname: Andria
authors.forename: C
authors.initials: C
authors.lastname: Petit
authors.forename: A
authors.initials: A
authors.lastname: Ballabio
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000595:Amino Acid Sequence; D001192:Arylsulfatases / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002806:Chondrodysplasia Punctata / Q000201:enzymology / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009928:Organ Specificity; D017354:Point Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014859:Warfarin / Q000009:adverse effects / Q000494:pharmacology*; D014960:X Chromosome
chemical_list: D012333:RNA, Messenger; D014859:Warfarin; C110155:ARSL protein, human; D001192:Arylsulfatases