两个粘多糖贮积症Ⅰ型家系IDUA基因的突变分析及产前诊断

IDUA gene mutation analysis and prenatal diagnosis of two families affected with mucopolysaccharidosis type Ⅰ

目的对两个粘多糖贮积症Ⅰ型（mucopolysaccharidosis type Ⅰ ,MPS Ⅰ）家系α—L-艾杜糖醛酸酶（α—L—iduronidase，IDUA）基因进行基因突变分析，为家系中的高危胎儿提供产前诊断。方法应用PCR扩增和直接双向测序分别对两个粘多糖贮积症Ⅰ型家系的先证者及其父母IDUA基因的14个外显子进行基因突变分析。基因突变确定后，抽取绒毛样本对家系胎儿进行产前诊断。结果测序结果显示家系1先证者存在IDUA基因第1外显子c．46-57delTCGCTCCTGGCC（p．Ser16_Ala19del）和第8外显子c．1147delC（p．Arg383Alafs＊57）复合杂合突变，先证者父亲为c．46—57delTCGCTCCTGGCC杂合突变携带者，先证者母亲为c．1147delC杂合突变携带者，先证者两个突变分别来自父母，前者为已知突变、后者为未报道过的新突变；产前诊断显示胎儿携带c．46—57delTcGcTccTGGc杂合缺失突变。家系2先证者存在IDUA基因第6外显子c．721T〉C（p．Cys241Arg）和第10外显子c．1491delG（p．Thr497fs27）复合杂合突变；先证者母亲为c．721T〉C错义杂合突变携带者，父亲为c．1491delG缺失杂合突变携带者，先证者的两个突变分别来自父母，均为未报道过的新突变，产前诊断显示胎儿携带c．721T〉C杂合错义突变。结论IDUA基因突变是2个粘多糖贮积症Ⅰ型家系的致病原因，我们的结果丰富了IDUA基因突变谱，为家系产前诊断提供了依据。

Objective To analyze mutations of IDUA gene in two pedigrees affected with mucopolysaccharidosis type Ⅰ and provide prenatal diagnosis for them. Methods The 14 exons of the IDUA gene were subjected to PCR amplification and Sanger sequencing. Results For pedigree 1, the proband was found to harbor compound heterozygous mutations c. 46-57delTCGCTCCTGGCC （p. Ser16_ Ala19del） of exon 1 and c. l147delC （p. Arg383Alafs ＊ 57） of exon 8 of the IDUA gene, which were inherited from his father and mother, respectively. The latter was unreported previously. Prenatal diagnosis suggested that the fetus has carried a heterozygous c. 46-57delTCGCTCCTGGCC mutation. For family 2, the proband was also found to carry compound mutations of the IDUA gene, namely c. 721T 〉 C （p. Cys241Arg） of exon 6 and c. 1491delG （p. Thr497fs27） of exon 8, which were inherited from her mother and father, respectively. Neither mutation was reported previously. Prenatal diagnosis suggested that the fetus has carried a heterozygous c. 721T〉C mutation. Conclusion Mutations of the IDUA gene probably underlie the MPS- Ⅰ in both pedigrees. Above results have enriched the spectrum of IDUA gene mutations and facilitated prenatal diagnosis for both families.