title: Molecular evaluation of a novel missense mutation & an insertional truncating mutation in SUMF1 gene.
abstract: OBJECTIVE
  Multiple suphphatase deficiency (MSD) is an autosomal recessive disorder affecting the post translational activation of all enzymes of the sulphatase family. To date, approximately 30 different mutations have been identified in the causative gene, sulfatase modifying factor 1 (SUMF1). We describe here the mutation analysis of a case of MSD.
  
  
  METHODS
  The proband was a four year old boy with developmental delay followed by neuroregression. He had coarse facies, appendicular hypertonia, truncal ataxia and ichthyosis limited to both lower limbs. Radiographs showed dysostosis multiplex. Clinical suspicion of MSD was confirmed by enzyme analysis of four enzymes of the sulphatase group.
  
  
  RESULTS
  The patient was compound heterozygote for a c.451A>G (p.K151E) substitution in exon 3 and a single base insertion mutation (c.690_691 InsT) in exon 5 in the SUMF1 gene. The bioinformatic analysis of the missense mutation revealed no apparent effect on the overall structure. However, the mutated 151-amino acid residue was found to be adjacent to the substrate binding and the active site residues, thereby affecting the substrate binding and/or catalytic activity, resulting in almost complete loss of enzyme function.
  
  
  CONCLUSIONS
  The two mutations identified in the present case were novel. This is perhaps the first report of an insertion mutation in SUMF1 causing premature truncation of the protein.
authors.forename: Udhaya H
authors.initials: UH
authors.lastname: Kotecha
authors.forename: Sireesha
authors.initials: S
authors.lastname: Movva
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Verma
authors.forename: Ratna Dua
authors.initials: RD
authors.lastname: Puri
authors.affiliation: Center of Medical Genetics, Sir Ganga Ram Hospital, New Delhi, India.
authors.forename: Ishwar Chander
authors.initials: IC
authors.lastname: Verma
mesh_terms: D002675:Child, Preschool; D019295:Computational Biology; D002658:Developmental Disabilities / Q000235:genetics*; D004413:Dysostoses / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D008297:Male; D052517:Multiple Sulfatase Deficiency Disease / Q000235:genetics*; D016254:Mutagenesis, Insertional / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D011859:Radiography; D013429:Sulfatases / Q000235:genetics* / Q000378:metabolism
chemical_list: D050862:Oxidoreductases Acting on Sulfur Group Donors; C480483:SUMF1 protein, human; D013429:Sulfatases