Update of the spectrum of mucopolysaccharidoses type III in Tunisia: identification of three novel mutations and in sili
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Update of the spectrum of mucopolysaccharidoses type III in Tunisia: identification of three novel mutations and in silico structural analysis of the missense mutations Souad Ouesleti, Maria Francisca Coutinho, Isaura Ribeiro, Abdehedi Miled, Dalila Saidane Mosbahi, Sandra Alves Porto, Portugal
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
Author Affiliations: Biochemical Service, CHU Farhat Hached, 4000, Sousse, Tunisia (Ouesleti S, Miled A); Research and Development Unit, Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge, Porto, Portugal (Coutinho MF, Alves S); Biochemical Genetics Unit, Medical Genetics Center Dr. Jacinto de Magalhães, Porto Hospital Centre, Porto, Portugal (Ribeiro I); Laboratory of Analysis, Treatment and Valorization of Pollutants of the Environment and Products. Faculty of Pharmacy, University of Monastir, 5000. Tunisia (Mosbahi DS) Corresponding Author: Sandra Alves, Research and Development Unit, Department of Human Genetics, INSA Rua Alexandre Herculano, 321,4000-055 Porto, Portugal (Tel: +351 223 401 100; Fax: +351223 401 109; Email: [email protected], [email protected]) doi: 10.1007/s12519-017-0005-x ©Children's Hospital, Zhejiang University School of Medicine, China and Springer-Verlag Berlin Heidelberg 2017. All rights reserved.
World J Pediatr, Online First, January 2017 . www.wjpch.com
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. World J Pediatr January 2017; Online First Key words: molecular characterization; mucopolysaccharidosis III mutation
Introduction
T
he mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders, caused by deficiency of enzymes catalyzing the stepwise d
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