Update of the spectrum of mucopolysaccharidoses type III in Tunisia: identification of three novel mutations and in silico structural analysis of the missense mutations

Ouesleti, Souad; Coutinho, Maria Francisca; Ribeiro, Isaura; Miled, Abdehedi; Mosbahi, Dalila Saidane; Alves, Sandra

Publication

Update of the spectrum of mucopolysaccharidoses type III in Tunisia: identification of three novel mutations and in silico structural analysis of the missense mutations

2017-01-19Journal article

dc.contributor.author	Ouesleti, Souad
dc.contributor.author	Coutinho, Maria Francisca
dc.contributor.author	Ribeiro, Isaura
dc.contributor.author	Miled, Abdehedi
dc.contributor.author	Mosbahi, Dalila Saidane
dc.contributor.author	Alves, Sandra
dc.date.accessioned	2017-02-20T14:18:23Z
dc.date.available	2018-01-20T01:30:09Z
dc.date.issued	2017-01-19
dc.description.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-N-acetylglucosaminidase (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. CONCLUSION: 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.	pt_PT
dc.description.sponsorship	This study was partially supported by Millennium bcp Foundation (bcp/LIM/DGH/2014). Coutinho MF is grantee from the Foundation for Science and Technology Portugal (SFRH/BPD/101965/2014)	pt_PT
dc.description.version	info:eu-repo/semantics/publishedVersion	pt_PT
dc.identifier.citation	World J Pediatr. 2017 Aug;13(4):374-380. doi: 10.1007/s12519-017-0005-x. Epub 2017 Jan 19.	pt_PT
dc.identifier.doi	10.1007/s12519-017-0005-x	pt_PT
dc.identifier.issn	1708-8569
dc.identifier.uri	http://hdl.handle.net/10400.18/4284
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Springer Verlag/ Children's Hospital, Zhejiang University School of Medicine, China	pt_PT
dc.relation.publisherversion	http://link.springer.com/article/10.1007%2Fs12519-017-0005-x	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by-nc/4.0/	pt_PT
dc.subject	Mucopolysaccharidosis III	pt_PT
dc.subject	Molecular Characterization	pt_PT
dc.subject	Mutation	pt_PT
dc.subject	Doenças Genéticas	pt_PT
dc.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	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.citation.title	World Journal of Pediatrics	pt_PT
rcaap.rights	embargoedAccess	pt_PT
rcaap.type	article	pt_PT