Identification of 11 novel mutations in 49 Korean patients with mucopolysaccharidosis type II

Sohn YB, Ki C‐S, Kim C‐H, Ko A‐R, Yook Y‐J, Lee S‐J, Kim SJ, Park SW, Yeau S, Kwon E‐K, Han SJ, Choi EW, Lee S‐Y, Kim J‐W, Jin D‐K. Identification of 11 novel mutations in 49 Korean patients with mucopolysaccharidosis type II. Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is a rare lysosomal storage disorder caused by a deficiency of iduronate‐2‐sulfatase (IDS). As MPS II is X‐linked, patients are usually males with heterogeneous mutations ranging from point mutations to gross deletions and recombination. In 2003, we reported a mutation analysis of 25 patients with MPS II. In this study, 31 mutations in another 49 Korean patients (45 families) with MPS II are reported: 12 missense, nine deletions, four splicing, two nonsense, two insertions, one deletion/insertion, and IDS‐IDS2 recombination mutations. Among these mutations, 11 were novel ones (4 missense mutations: Ser61Pro, Pro97Arg, Pro228Ala, and Pro261Ala; 5 deletions: c.344delA, c.420delG, c.768delT, c.1112delC and c.1402delC; 1 deletion/insertion: c.1222delinsTA; and 1 insertion mutation: c.359_360insATCC). The IDS‐IDS2 recombination mutations were most frequently observed; all patients with this mutation had the severe MPS II phenotype. However, most of the patients (5/7) with the G374G splicing mutation had an attenuated phenotype, except for two sibling cases with the severe phenotype. Except for a few recurrent mutations such as the G374G, R443X, L522P, and recombination mutations, each patient had a unique individual mutation. Therefore, careful interpretation of genotype–phenotype correlations is warranted.