title: The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases.
abstract: In multiple sulfatase deficiency (MSD), a human inherited disorder, the activities of all sulfatases are impaired due to a defect in posttranslational modification. Here we report the identification, by functional complementation using microcell-mediated chromosome transfer, of a gene that is mutated in MSD and is able to rescue the enzymatic deficiency in patients' cell lines. Functional conservation of this gene was observed among distantly related species, suggesting a critical biological role. Coexpression of SUMF1 with sulfatases results in a strikingly synergistic increase of enzymatic activity, indicating that SUMF1 is both an essential and a limiting factor for sulfatases. These data have profound implications on the feasibility of enzyme replacement therapy for eight distinct inborn errors of metabolism.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cosma
authors.forename: Stefano
authors.initials: S
authors.lastname: Pepe
authors.forename: Ida
authors.initials: I
authors.lastname: Annunziata
authors.forename: Robert F
authors.initials: RF
authors.lastname: Newbold
authors.forename: Markus
authors.initials: M
authors.lastname: Grompe
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Parenti
authors.forename: Andrea
authors.initials: A
authors.lastname: Ballabio
mesh_terms: D000818:Animals; D019556:COS Cells; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D019143:Evolution, Molecular; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013106:Sphingolipidoses / Q000201:enzymology* / Q000235:genetics*; D013429:Sulfatases / Q000172:deficiency* / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D013429:Sulfatases