21-羟化酶缺乏症的分子诊断及临床意义

doi:10.3969/j.issn.1674-8115.2022.05.001

上海交通大学学报（医学版） ›› 2022, Vol. 42 ›› Issue (5): 557-561.doi: 10.3969/j.issn.1674-8115.2022.05.001

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21-羟化酶缺乏症的分子诊断及临床意义

吕拥芬(), 李嫔()

上海市儿童医院，上海交通大学医学院附属儿童医院内分泌科，上海 200062

收稿日期:2022-03-11 接受日期:2022-04-27 出版日期:2022-05-28 发布日期:2022-05-28
通讯作者: 李嫔 E-mail:lvyf@shchildren.com.cn;lipin21@126.com
作者简介:吕拥芬（1974—），女，副主任医师，硕士；电子信箱：lvyf@shchildren.com.cn。
基金资助:
国家自然科学基金(81871131)

Molecular diagnosis and clinical significance of 21-hydroxylase deficiency

LÜ Yongfen(), LI Pin()

Department of Endocrinology, Shanghai Children's Hospital, Children's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200062, China

Received:2022-03-11 Accepted:2022-04-27 Online:2022-05-28 Published:2022-05-28
Contact: LI Pin E-mail:lvyf@shchildren.com.cn;lipin21@126.com
Supported by:
National Natural Science Foundation of China(81871131)

摘要/Abstract

摘要：

21-羟化酶缺乏症是先天性肾上腺皮质增生症最常见的类型。目前的诊断主要依据临床症状和实验室检测，容易发生误诊或漏诊且无法对患者的基因型进行分析。进行CYP21A2基因检测有助于该病的确诊；但由于该基因组区域具有高度变异性，其分子遗传学诊断比许多其他单基因遗传病更为复杂。95%的致病变异是由于功能基因与假基因间重组所致；最常见的变异有10种，包括大片段的缺失和基因转换、8种CYP21A2与CYP21A1P来源的点突变（p. P30L、I2G、p. I172N、E6 cluster、p. V281L、F306+T、p.Q318X、p.R356W）、外显子3的p.G110fs（8个碱基缺失）。最佳的基因分析应该是基于聚合酶链反应的序列分析联合多重连接探针扩增技术。由于该病基因型与表型之间有良好的相关性，在大多数情况下可以通过基因型预测临床表型的严重程度并指导治疗及遗传咨询。

关键词: 21-羟化酶缺乏症, CYP21A2基因, 分子诊断

Abstract:

21-hydroxylase deficiency is the most common type of congenital adrenal hyperplasia. Currently, diagnosis is mainly based on clinical symptoms and biochemical tests, but misdiagnosis or missed diagnosis is prone to occur and genotype analysis of patients is not possible. Testing for CYP21A2 can help confirm the diagnosis of the disease, but molecular genetic diagnosis is more complex than many other single-gene disorders due to the high variability of the 21-hydroxylase genome region. There are 95% of pathogenic mutations due to recombination between functional gene and pseudogene, with 10 of the most common variants including large deletions and and gene conversions, 8 point pathogenic variants of CYP21A2 and CYP21A1P (p.P30L, I2G, p.I172N, E6 cluster, p.V281L, F306+T, p.Q318X, and p.R356 W), and p.G110fs (8 bp deletion) of exons 3. Best practice genotyping should be polymerase chain reaction (PCR)-based sequence analysis along with multiplex ligation-dependent probe amplification. Because there is a good correlation between genotype and phenotype, genotype can be used to predict the severity of clinical phenotype and guide treatment and genetic counseling in most cases.

Key words: 21- hydroxylase deficiency, CYP21A2 gene, molecular diagnosis

中图分类号:

R725.8

吕拥芬, 李嫔. 21-羟化酶缺乏症的分子诊断及临床意义[J]. 上海交通大学学报（医学版）, 2022, 42(5): 557-561.

LÜ Yongfen, LI Pin. Molecular diagnosis and clinical significance of 21-hydroxylase deficiency[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(5): 557-561.

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21-羟化酶缺乏症的分子诊断及临床意义

Molecular diagnosis and clinical significance of 21-hydroxylase deficiency

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