Update of the spectrum of mucopolysaccharidoses type III in Tunisia: identification of three novel mutations and in silico structural analysis of the missense mutations.
World J Pediatr
; 13(4): 374-380, 2017 Aug.
Article
en En
| MEDLINE
| ID: mdl-28101780
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.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Análisis Mutacional de ADN
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Mucopolisacaridosis III
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Predisposición Genética a la Enfermedad
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Mutación Missense
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
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Prognostic_studies
Límite:
Female
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Humans
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Male
/
Newborn
País/Región como asunto:
Africa
Idioma:
En
Revista:
World J Pediatr
Asunto de la revista:
PEDIATRIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Túnez