MUCOPOLYSACCHARIDOSIS TYPE-II (HUNTER-DISEASE) - IDENTIFICATION AND CHARACTERIZATION OF 8-POINT MUTATIONS IN THE IDURONATE-2-SULFATASE GENE IN JAPANESE PATIENTS

作者：SUKEGAWA K^*; TOMATSU S; FUKAO T; IWATA H; SONG XQ; YAMADA Y; FUKUDA S; ISOGAI K; ORII T

来源：Human Mutation, 1995, 6(2): 136-143.

DOI：10.1002/humu.1380060206

• MUCOPOLYSACCHARIDOSIS TYPE II
• HUNTER DISEASE
• IDURONATE-2 SULFATASE
• WESTERN BLOT
• MUTATION ANALYSIS

Mucopolysaccharidosis type II (Hunter disease) is a lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. Varied clinical phenotypes of this disease have been described. To identify mutations in individual patients and to examine possible correlations between mutations and clinical phenotypes, we analyzed the iduronate-2-sulfatase gene in Japanese patients with different clinical phenotypes. Five missense mutations, S333L (severe), R468Q (severe), R468L (severe), W337R (intermediate), R48P (mild), and three nonsense mutations, W345X (severe), R443X (intermediate), Q531X (mild), were identified by the RT PCR method. Transient expression in the enzyme deficient fibroblasts revealed that all five missense mutant enzymes were synthesized as the normal-size precursor (13 kD), and the nonsense mutant enzymes were synthesized as truncated ones (W345X:54 kD, R443X:59 kD, and Q531X:69 kD), although stable mature enzymes (45-56 kD) were not detected by Western blot analysis. Furthermore, expression of the eight mutant cDNAs resulted in severe reductions of iduronate-2-sulfatase enzyme activity in comparison with a normal cDNA.

• 出版日期1995