21-羟化酶缺乏症基因型和临床表型分析

摘要

目的了解21-羟化酶缺乏症（21-OHD）患儿CYP21A2基因突变热点，并分析其基因型和表型的关系。方法对在新生儿17α羟孕酮（17-α OHP）筛查中发现并诊断的18例21-OHD患儿及其父母，采用等位基因特异性PCR-直接测序联合多重连接依赖探针扩增技术测定其基因型。结果共检出6种CYP21A2基因突变类型，最常见的为I2G（44.4%）和del（33.3%），这两种也是失盐型常见的突变；单纯男性化型患儿I172N突变检出率达75%。根据对21-羟化酶活性影响程度将患儿分为重度、中度和轻度组，三组间反映病情严重性的指标17-α OHP、促肾上腺皮质激素、睾酮的差异均有统计学意义（P<0.05）。结论21-OHD基因诊断技术的建立揭示了基因型和临床表型的一致性。%Objectives To study the mutation spectrum in CYP21A2 gene in patients with 21-hydroxylase deficiency (21-OHD), and to analyze the relationship between genotype and phenotype. Methods Eighteen patients with 21-OHD were identified by neonatal screening of 17α-OH progesterone (17α-OHP). The allele specific PCR-DNA sequencing com-bining with multiplex ligation-dependent probe amplification was applied to determine the genotype in the patients and their parents. Results Six mutations of CYP21A2 gene were identified. I2G (44.4%) and del (33.3%) were the most frequent mutations and also were the most common mutations in salt-wasting form. The detection rate of I172N mutation in simple virilizing form was 75%. Patients were classified into three groups according to the degree of 21-hydroxylase enzymatic compromise caused by the mutation. The serum 17α-OHP, ACTH and T levels which reflected the severity of disease were significantly different among three groups (P<0.05). Conclusions The genetic diagnosis of 21-OHD reveals the consistency between genotype and phenotype.