Background:Mucopolysaccharidoses type Ⅲ (MPS Ⅲ) are a group of autosomai recessive lysosomal storage diseases,caused by mutations in genes that code for enzymes involved in the lysosomal degradation of heparan sulph...Background:Mucopolysaccharidoses type Ⅲ (MPS Ⅲ) are a group of autosomai 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),a-N-acetylglucosaminidase (NAGLU),heparan sulfate acetyl-CoA:a-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.展开更多
文摘Background:Mucopolysaccharidoses type Ⅲ (MPS Ⅲ) are a group of autosomai 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),a-N-acetylglucosaminidase (NAGLU),heparan sulfate acetyl-CoA:a-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.
