Mutation analysis of exon 8 of the iduronate-2-sulfatase gene in mucopolysaccharidosis type II patients in Indonesia

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.