Mutational spectrum of the iduronate 2 sulfatase gene in 25 unrelated Korean Hunter syndrome patients: identification of 13 novel mutations.
Hunter syndrome (Mucopolysaccharidosis type II, MPS2) is an X-linked recessively inherited disease caused by a deficiency of iduronate 2 sulfatase (IDS). In this study, we investigated mutations of the IDS gene in 25 Korean Hunter syndrome patients. We identified 20 mutations, of which 13 mutations are novel; 6 small deletions (69_88delCCTCGGATCCGAAACGCAGG, 121-123delCTC, 500delA, 877_878delCA, 787delG, 1042_1049delTACAGCAA), 2 insertions (21_22insG, 683_684insC), 2 terminations (529G>T, 637A>T), and 3 missense mutations (353C>A, 779T>C, 899G>T). Moreover, using TaqI or HindIII RFLPs, we found three gene deletions. When the 20 mutations were depicted in a 3-dimensional model of IDS protein, most of the mutations were found to be at structurally critical points that could interfere with refolding of the protein, although they were located in peripheral areas. We hope that these findings will further the understanding of the underlying mechanisms associated with the disease.
Kim
Chi Hwa
CH
Clinical Research Center, Samsung Biomedical Research Center, Seoul, Korea.
Hwang
Hye Zin
HZ
Song
Seng Mi
SM
Paik
Kyung Hoon
KH
Kwon
Eun Kyung
EK
Moon
Kwang Bin
KB
Yoon
Jeong Hyeok
JH
Han
Cheol Kyu
CK
Jin
Dong-Kyu
DK
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D006801:Humans; D007066:Iduronate Sulfatase / Q000737:chemistry / Q000235:genetics*; D007723:Korea / Q000453:epidemiology; D008958:Models, Molecular; D016532:Mucopolysaccharidosis II / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D009154:Mutation; D020836:Protein Structure, Quaternary / Q000235:genetics
D004247:DNA; D007066:Iduronate Sulfatase