Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical Approach.
Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical Approach.
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DOI：
10.3389/fendo.2022.834549
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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作者：
儿科患者的肾上腺功能不全主要是由于先天性肾上腺增生（CAH），这是一种严重的单基因疾病，95%的病例由类固醇21-羟化酶缺乏症（21-OHD，由CYP 21 A2基因编码）引起。CYP 21 A2基因分型需要仔细的分析，以保证基因特异性PCR，准确定义假基因-基因嵌合体，基因重复和避免等位基因丢失。一小组明确的致病性改变不仅在有症状的患者中，而且在17-羟孕酮的边界/阳性结果的无症状患者中，在确认/排除疾病方面具有高诊断率。不幸的是，这个基因座的复杂性使得它今天不愿意大规模测序的高通量技术。分子改变和酶缺乏程度之间存在的密切关系使遗传研究能够证明其在预测/分类疾病临床形式方面的有用性。其他方面的利益，关于分子研究包括其独立的生理变异和分析干扰，其在诊断男性的简单男性化形式的有用性和其固有的贡献，遗传咨询，一个非常重要的方面，考虑到高载波频率CAH在一般人群。CYP 21 A2的基因检测是一种不可替代的工具，不仅可以检测经典形式的家庭成员中的严重等位基因，还可以检测疾病和夫妇的轻度迟发性形式。它在辅助生殖和植入前诊断等领域也很有帮助。在专家知识下对21-OHD进行分子诊断肯定有助于在临床过程的每一步更好地管理疾病。
Adrenal insufficiency in paediatric patients is mostly due to congenital adrenal hyperplasia (CAH), a severe monogenic disease caused by steroid 21-hydroxylase deficiency (21-OHD, encoded by the CYP21A2 gene) in 95% of cases. CYP21A2 genotyping requires careful analyses that guaranty gene-specific PCR, accurate definition of pseudogene-gene chimeras, gene duplications and allele dropout avoidance. A small panel of well-established disease-causing alterations enables a high diagnostic yield in confirming/discarding the disorder not only in symptomatic patients but also in those asymptomatic with borderline/positive results of 17-hydroxyprogesterone. Unfortunately, the complexity of this locus makes it today reluctant to high throughput techniques of massive sequencing. The strong relationship existing between the molecular alterations and the degree of enzymatic deficiency has allowed genetic studies to demonstrate its usefulness in predicting/classifying the clinical form of the disease. Other aspects of interest regarding molecular studies include its independence of physiological variations and analytical interferences, its usefulness in the diagnosis of simple virilizing forms in males and its inherent contribution to the genetic counseling, an aspect of great importance taking into account the high carrier frequency of CAH in the general population. Genetic testing of CYP21A2 constitutes an irreplaceable tool to detect severe alleles not just in family members of classical forms but also in mild late-onset forms of the disease and couples. It is also helpful in areas such as assisted reproduction and preimplantation diagnosis. Molecular diagnosis of 21-OHD under expert knowledge definitely contributes to a better management of the disease in every step of the clinical course.
影响因子：
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作者：
Sweeten TL;Odell DW;Odell JD;Torres AR
通讯作者：
Torres AR