Characterization of point mutations in patients with X-linked ichthyosis: Effects on the structure and function of the steroid sulfatase protein

Elisabeth S. Alperin, Larry J. Shapiro

    Research output: Contribution to journalArticle

    57 Scopus citations

    Abstract

    X-linked ichthyosis is the result of steroid sulfatase (STS) deficiency. While most affected individuals have extensive deletions of the STS gene, point mutations have been reported in three patients (1). In this study, we identify an additional three point mutations and characterize the effects of all six mutations on STS activity and expression. All six are unique single base pair substitutions. The mutations are located in a 105-amino acid region of the C-terminal half of the polypeptide. Five of the six mutations involve the substitutions of Pro or Arg for Trp372, Arg for His444, Tyr for Cys446, or Leu for Cys341. The other mutation is in a splice junction and results in a frameshift causing premature termination of the polypeptide at residue 427. All the affected residues are conserved to some degree within the sulfatase family. The six mutations were reproduced in normal STS cDNA and transiently expressed in STS-deficient cells. All six mutant vectors direct the expression of STS protein that lacks enzymatic activity. The mutant polypeptides show a shift in mobility on SDS-PAGE and resistance to proteinase K digestion when translated in the presence of dog pancreas microsomes, indicating glycosylation and normal translocation.

    Original languageEnglish
    Pages (from-to)20756-20763
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume272
    Issue number33
    DOIs
    StatePublished - Aug 15 1997

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