Anggia Nurwulan Kusno Putri1, Rizky Priambodo2, Yulia Ariani3, Steven Arianto4, Damayanti Rusli Sjarif5
1Human Genetic Research Center, Indonesian Medical Education and Research Institute; Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Jakarta, Indonesia
2Human Genetic Research Center, Indonesian Medical Education and Research Institute, Universitas Indonesia, Jakarta, Indonesia
3Human Genetic Research Center, Indonesian Medical Education and Research Institute; Department of Pediatric, Faculty of Medicine, Cipto Mangunkusumo National Referral Hospital; Department of Medical Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
4Human Genetic Research Center, Indonesian Medical Education and Research Institute; Department of Biology, Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
5Human Genetic Research Center, Indonesian Medical Education and Research Institute; Department of Pediatric, Faculty of Medicine, Cipto Mangunkusumo National Referral Hospital, Universitas Indonesia, Jakarta, Indonesia.
DOI: 10.4103/jnsbm.JNSBM_44_19
ABSTRACT
Objective: Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is a rare, recessive, X-linked lysosomal storage disorder caused by a deficiency of lysosomal enzyme iduronate-2-sulfatase (IDS), encoded by IDS gene. I2S plays an important role in the lysosomal degradation of dermatan sulfate and heparan sulfate, with I2S deficiency leading to the accumulation of these glycosaminoglycans in the tissues. Materials and Methods: Exon-specific analyses of IDS exon 8 from eight Indonesian patients with MPS II from Cipto Mangunkusumo Hospital, Jakarta, Indonesia, were performed using polymerase chain reaction and sequencing-based methods. Results: Two novel mutations and a deletion variant of exon 8 were identified among the patients. A single-nucleotide deletion variant (c.1023delA), causing a frameshift in the corresponding amino acid sequence (p.Glu341AspfsTer19), was observed in all patients. In addition, a novel missense mutation (c.1033T>C) resulting in a tryptophan to arginine substitution (p.Trp345Arg), along with a single-nucleotide deletion (c.1041delA) resulting in a second frameshift in the amino acid sequence (p.Lys347AsnfsTer13), was also observed in one patient. Conclusion: This study provides the first mutation analysis of exon 8 of IDS and successfully identified mutations within the IDS gene that may be associated with MPS II. These findings will be added to the IDS gene profile database and may help in the diagnosis of MPS II in future.
Keywords: Deletion, exon 8, IDS gene, lysosomal storage disorder, missense, mucopolysaccharidosis II, novel mutation, polymerase chain reaction.
