中国人粘多糖贮积症Ⅰ型IDUA基因突变的检测

Mutations Analysis of IDUA Gene in Chinese Mucopolysacchridosis TypeⅠPatients

【目的】检测中国人粘多糖贮积症Ⅰ型患者IDUA基因 (IDUA )突变。【方法】采用PCR SSCP、PCR产物直接测序等技术对 35例粘多糖贮积症Ⅰ型患者的IDUA第 2、6、7、8、9和 10外显子及其相邻区域进行突变筛查。【结果】本研究筛查出 7种突变 ,均为单碱基置换。一内含子区突变nt1486C→T ;一中性突变nt1945G→C ;1种无义突变E40 4X ;4种错义突变 :F198L、L2 18V、A36 1T和V45 4I。【结论】中国人IDUA在第 2、6、7、8、9和 10外显子区存在突变。在上述检测到的 7种突变中 ,A36 1T国外已确定为多态性 ,E40 4X国外已报道为重型突变。而nt1486C→T、F198L和L2 18V和V45 4I为我们首次发现和报道 ,可能为新突变 ,但其突变性质还有待于进一步鉴定。

To screen the mutation of IDUA gene (IDUA) in Chinese patients with MPS I. Using PCR SSCP and directly sequencing techniques, the 2, 6, 7, 8, 9 and 10 exons and the adjacent regions of IDUA were screened for 35 MPS I patients. In this study, 7 mutations have been found, which are al1 base substitutions. One mutation is in the intron 5: nt1486C→T; One same sense mutation in exon 7: nt1945G→C; One nonsense mutationand in exon 9: E404X; 4 missense mutations: A361T (exon 8), F198L (exon 6), L218V (exon 6) and V454I (exon 9). [Conclusion] The exons 2, 6, 7, 8, 9 and 10 of IDUA gene have mutations among the Chinese. Out of the 7 mutations we have found, A361T and V454I has been identified as polymorphic site, and nt1945G→C is a same sense mutation. E404X have been reported as a severe mutation in abroad. However, nt1486C→T, F198L, L218V and V454I are first reported by us. These 4 mutations may be pathogenic mutations, which needs further identification.