A Novel mutation in iduronate-2-sulfatase gene Exon 6 of an Indonesian patient with Mucopolysaccharidosis type II

Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare X-linked recessive disease caused mutation of the gene encoding the lysosomal enzyme iduronate-2-sulfatase (IDS). Deficient lysosomal degradation of the glycosaminoglycans dermatan sulfate and heparan sulfate by mutant IDS leads to their accumulation in multiple tissues, causing progressive tissue hypertrophy (e.g., hepatosplenomegaly and macroglossia), various deformities, and narrowing of the respiratory tract among other symptoms. Here, we searched from additional IDS mutations in Indonesian patients to provide information for establishing associations with disease traits. Exon-specific PCR amplification and sequencing of IDS gene exon 6 were conducted on DNA samples from MPS II patients and healthy controls at Cipto Mangunkusumo National Referral Hospital, Jakarta, Indonesia. A novel mutation in an Indonesian patient with MPS II was identified, a 14 bp insertion mutation (c.792_793insCCCCTGTGGCCTAC) in IDS gene exon 6 resulting in the amino acid changes p.Tyr264_X269insProLeuTrpPro and X269Thr. This novel mutation likely alters the structure and function of IDS. We are currently analyzing other IDS gene exons to identify additional mutations linked to IDS. Such studies will help clarify MPS II pathophysiology and may lead to novel treatment strategies.