Wilson病ATP7B基因Arg778Leu突变与临床表型之相关性探讨

A study on the relationship between Arg778leu mutation of ATP7B gene and clinical phenotype in Wilson disease patients

目的了解Ｗｉｌｓｏｎ病ＡＴＰ７Ｂ基因的突变与临床表现型的相关性。方法采用ＰＣＲ、ＭｓｐＩ酶消化和ＤＮＡ测序等技术对来自５１个家庭的５４例Ｗｉｌｓｏｎ病患者进行ＡＴＰ７Ｂ基因外显子８Ａｒｇ７７８Ｌｅｕ的检测。结果５４例Ｗｉｌｓｏｎ病患者中３６例存在Ａｒｇ７７８Ｌｅｕ（ＣＧＧ→ＣＴＧ）基因突变，１５例为纯合型，２１例为杂合型，Ａｒｇ７７８Ｌｅｕ等位基因突变频率为４７２％；４６例伴肝损害的患者中３３例存在ＡＴＰ７Ｂ基因外显子８的Ａｒｇ７７８Ｌｅｕ突变；３６例Ａｒｇ７７８Ｌｅｕ突变者中３４例同时伴有Ｌｅｕ７７０Ｌｅｕ多态性。结论Ａｒｇ７７８Ｌｅｕ突变类型是中国人Ｗｉｌｓｏｎ病的高频率突变点（４７２％）；Ａｒｇ７７８Ｌｅｕ突变基因型多数与肝损害临床型相关。

Objective To study the relationship between Arg778leu mutation of ATP7B gene and clinical phenotype of Wilson disease (WD) Methods Using PCR, Msp I digestion and DNA sequencing, the authors identified the Arg778leu mutations in exon 8 of ATP7B gene in 54 patients from 51 families Results Among 54 WD patients, 36 were found to carry Arg778leu (CGGCTG ) mutation, among whom 15 were homozygote, 21 were heterozygote, the frequency of this mutation was 472% Of 46 patients with hepatic damage, 36 were found to have the mutation of Arg778Leu, among whom 34 were found to have Leu770Leu polymorphism simultaneously Conclusion This study showed that there was a high frequency (472%) of Arg778leu mutation in WD patients The genotype of Arg778leu mutation correlated in most WD patients to the phenotype of hepatic damage