目的 探讨新疆维吾尔族儿童21-羟化酶缺乏症(21-OHD)基因突变规律及基因型和临床表型的关系。方法 选取2013年10月至2014年10月就诊的20例维吾尔族21-OHD患儿为研究对象,联合应用全长直接测序法和多重连接依赖探针扩增技术检测21-羟化酶编码基因CYP21A2的突变类型,并按照基因突变类型将21-OHD患者分成不同的组别,比较预期的临床表型和实际临床表型的一致性。结果 20例患儿共发现9种突变,其中8种为已确定的致病突变,分别为Del、conv、I2g、I172N、Cluster E6、8-bp del、V281L、R356W,另1种突变为内含子5上的新发突变(c.648+37A>G),目前尚未有相关文献报道,暂不明确是否具有病理性意义。大部分根据基因突变类型预测的临床表型与实际的临床表型符合率较高(67%以上),根据P30L、V281L突变预测的临床表型与实际临床表型符合率较低(33%)。结论 21-OHD的基因型与表型有较好的相关性,通过检测患者的基因型可以预测疾病的临床表型;新发突变(c.648+37A>G)可能与21-OHD的发病有一定的关系。
Abstract
Objective To investigate gene mutations and the relationship between genotypes and clinical phenotypes in Uygur children with 21-hydroxylase deficiency(21-OHD) in Xinjiang, China.Methods A total of 20 Uygur children with 21-OHD who visited the hospital between October 2013 and October 2014 were enrolled.Fulllength direct sequencing and multiplex ligation-dependent probe amplification(MLPA) were used to detect the mutations of CYP21A2 gene, which encoded 21-hydroxylase.According to the type of mutation, the patients with 21-OHD were divided into different groups to analyze the consistency between predicted clinical phenotypes and actual clinical phenotypes.Results A total of 9 mutation types were found in the 20 patients, and 8 of them were identified as pathogenic mutations, i.e., Del, conv, I2g, I172N, Cluster E6, 8-bp del, V281L, and R356W.The other mutation is the new mutation occurring in intron 5(c.648+37A>G), which had not been reported, and its pathological significance remains unknown.Most clinical phenotypes predicted by mutation types had a higher coincidence rate with actual clinical phenotypes(above 67%), and the clinical phenotypes predicted by P30L and V281L had a lower coincidence rate with actual clinical phenotypes(below 33%).Conclusions The genotype of 21-OHD has a good correlation with phenotype, and the clinical phenotype can be predicted by detecting the patient's genotype.The new mutation(c.648+37A>G) may be related to the pathogenesis of 21-OHD.
关键词
维吾尔族 /
21-羟化酶缺乏症 /
基因型 /
表型 /
儿童
Key words
Uygur /
21-Hydroxylase deficiency /
Genotype /
Phenotype /
Child
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