Abstract:

In the present study, through PCR amplification and direct sequencing of mutation “hotspots”, we were able to identify two novel mutations in the human iduronate-2-sulfatase (IDS) gene in two patients from unrelated families with mucopolysaccharidosis typeⅡ(MPSⅡ). The novel mutation IVS 6 -1g→a affected the 3′ splice acceptor site of intron 6, and was predicted to result in exon skipping. The novel mutation c.1587-1588 ins T involved a single base insertion be-tween nucleotides 1,587 and 1,588 in exon 9, and was predicted to result in frame shift and premature termination. The two novel mutations did not occur in 6 other unrelated MPS patients or in 100 alleles from normal individuals, indicating that they were not polymorphisms. The PCR-restriction enzyme digestion showed that the two newly identified mutations were of maternal origin, which was consistent with the X-linked recessive disorder. These findings suggest that the IDS gene mutations could be detected by amplifying mutation “hotspots”, direct sequencing and restriction digestion analysis, and the newly identified mutations may be disease-causing.