title: Update of the spectrum of mucopolysaccharidoses type III in Tunisia: identification of three novel mutations and in silico structural analysis of the missense mutations.
abstract: BACKGROUND
  Mucopolysaccharidoses type III (MPS III) are a group of autosomal recessive lysosomal storage diseases, caused by mutations in genes that code for enzymes involved in the lysosomal degradation of heparan sulphate: heparan sulfate sulfamidase (SGSH), α-Nacetylglucosaminidase (NAGLU), heparan sulfate acetyl-CoA: α-glucosaminide N-acetyltransferase (HGSNAT), and N-acetylglucosamine-6-sulfatase (GNS).
  
  
  METHODS
  In this study, we have performed the molecular analysis of the SGSH, NAGLU and HGSNAT genes in 10 patients from 6 different MPS III Tunisian families.
  
  
  RESULTS
  In the SGSH gene, two mutations were identified: one novel (p.D477N) and one already described (p.Q365X). In the NAGLU gene, two novel mutations were discovered (p.L550P and p.E153X). For the novel missense mutations found in these two genes we performed an in silico structural analysis and the results were consistent with the clinical course of the patients harboring those mutations. Finally, in HGSNAT gene, we found the splicesite mutation c.234+1G>A that had already been reported as relatively frequent in MPS IIIC patients from countries surrounding the basin of the Mediterranean sea. Its presence in two Tunisian MPS IIIC families points to the hypothesis of its peri Mediterranean origin. With the exception of the c.234+1G>A mutation, that was identified in two unrelated MPS IIIC families, the other identified mutations were family-specific and were always found in homozygosity in the patients studied, thus reflecting the existence of consanguinity in MPS III Tunisian families.
  
  
  CONCLUSIONS
  Three novel mutations are reported here, further contributing to the knowledge of the molecular basis of these diseases. The results of this study will allow carrier detection in affected families and prenatal molecular diagnosis, leading to an improvement in genetic counseling.
authors.affiliation: Biochemical Service, CHU Farhat Hached, 4000, Sousse, Tunisia.
authors.forename: Souad
authors.initials: S
authors.lastname: Ouesleti
authors.affiliation: Research and Development Unit, Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge, Porto, Portugal.
authors.forename: Maria Francisca
authors.initials: MF
authors.lastname: Coutinho
authors.affiliation: Biochemical Genetics Unit, Medical Genetics Center Dr. Jacinto de Magalhães, Porto Hospital Centre, Porto, Portugal.
authors.forename: Isaura
authors.initials: I
authors.lastname: Ribeiro
authors.affiliation: Biochemical Service, CHU Farhat Hached, 4000, Sousse, Tunisia.
authors.forename: Abdehedi
authors.initials: A
authors.lastname: Miled
authors.affiliation: Laboratory of Analysis, Treatment and Valorization of Pollutants of the Environment and Products, Faculty of Pharmacy, University of Monastir, Monastir, 5000, Tunisia.
authors.forename: Dalila Saidane
authors.initials: DS
authors.lastname: Mosbahi
authors.affiliation: Research and Development Unit, Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge, Porto, Portugal. sandra.alves@insa.min-saude.pt.|Research and Development Unit, Department of Human Genetics, INSA, Rua Alexandre Herculano, 321, 4000-055, Porto, Portugal. sandra.alves@insa.min-saude.pt.
authors.forename: Sandra
authors.initials: S
authors.lastname: Alves
mesh_terms: D000118:Acetylglucosaminidase / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D007231:Infant, Newborn; D008297:Male; D009084:Mucopolysaccharidosis III / Q000175:diagnosis* / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D018570:Risk Assessment; D012494:Sampling Studies; D014416:Tunisia
chemical_list: D006867:Hydrolases; C022708:N-sulfoglucosamine sulfohydrolase; C033079:alpha-N-acetyl-D-glucosaminidase; D000118:Acetylglucosaminidase
keywords: molecular characterization; mucopolysaccharidosis III mutation