title: Clinical and mutational characterization of three patients with multiple sulfatase deficiency: report of a new splicing mutation.
abstract: Multiple sulfatase deficiency (MSD) is a rare autosomal recessive lysosomal storage disease characterized by impaired activity of all known sulfatases. The gene SUMF1, recently identified, encodes the enzyme responsible for post-translational modification of a cysteine residue, which is essential for the activity of sulfatases. Fewer than 30 MSD patients have been reported to date and 23 different mutations in the SUMF1 gene have been identified. Here, we present the characterization of the mutant alleles of two Spanish and one Argentinean MSD patients. While the two Spanish patients were homozygous for the previously described mutations, c.463T>C (p.S155P) and c.1033C>T (p.R345C), the Argentinean patient was homozygous for the new mutation IVS7+5 G>T. A minigene approach was used to analyze the effect of the splice site mutation identified, due to the lack of sample from the patient. This experiment showed that this change altered the normal splicing of the RNA, which strongly suggests that this is the molecular cause of the disease in this patient.
authors.affiliation: Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Díaz-Font
authors.forename: Raül
authors.initials: R
authors.lastname: Santamaría
authors.forename: Mònica
authors.initials: M
authors.lastname: Cozar
authors.forename: Mariana
authors.initials: M
authors.lastname: Blanco
authors.forename: Néstor
authors.initials: N
authors.lastname: Chamoles
authors.forename: Maria Josep
authors.initials: MJ
authors.lastname: Coll
authors.forename: Amparo
authors.initials: A
authors.lastname: Chabás
authors.forename: Lluïsa
authors.initials: L
authors.lastname: Vilageliu
authors.forename: Daniel
authors.initials: D
authors.lastname: Grinberg
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D050862:Oxidoreductases Acting on Sulfur Group Donors; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D013106:Sphingolipidoses / Q000235:genetics* / Q000473:pathology*; D013429:Sulfatases / Q000235:genetics
chemical_list: D017931:DNA Primers; D050862:Oxidoreductases Acting on Sulfur Group Donors; C480483:SUMF1 protein, human; D013429:Sulfatases