Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy.
Mol Diagn Ther. 2019 Oct;23(5):563-567. doi: 10.1007/s40291-019-00415-z.
More than 95% of congenital adrenal hyperplasia (CAH) cases are associated with mutations in the 21-hydroxylase gene (CYP21A2) in the human leukocyte antigen (HLA) class III area on the short arm of chromosome 6p21.3. In the diagnosis of 21-hydroxylase deficiency, CYP21A2 genotyping is a valuable complement to biochemical investigations. Genotyping can confirm the diagnosis (or carrier state) and, at the same time, provide accurate phenotype prediction in patients carrying severe mutations. In addition, the use of genetic testing is also helpful in prenatal diagnosis where the goal of prenatal treatment is preventing genital virilization of the female fetus. An in-depth knowledge of CYP21A2 genetics is essential to assure the correct interpretation of results obtained. To date, more than 200 small pathogenic variants of the CYP21A2 gene have been reported, showing good agreement between clinical phenotype and patient genotype. Recently, novel CYP21A2 deletions, involving one or more exons, have been reported in different populations. Since these rearrangements have never been described before in the genetic history of 21-hydroxylase deficiency, these new deletions have aroused particular interest. However, it is possible that these novel rearrangements are the result of incorrect interpretation of multiplex ligation-dependent probe amplification (MLPA).
超过 95%的先天性肾上腺皮质增生症（CAH）病例与人类白细胞抗原（HLA）III 类区域第 6 号染色体短臂 6p21.3 上的 21-羟化酶基因（CYP21A2）突变有关。在 21-羟化酶缺乏症的诊断中，CYP21A2 基因分型是生化研究的有益补充。基因分型可以确认诊断（或携带者状态），同时为携带严重突变的患者提供准确的表型预测。此外，遗传检测的使用也有助于产前诊断，其中产前治疗的目标是防止女性胎儿的生殖器男性化。深入了解 CYP21A2 遗传学对于确保正确解释获得的结果至关重要。迄今为止，已经报道了超过 200 种 CYP21A2 基因的小致病性变体，其临床表型与患者基因型之间具有良好的一致性。最近，在不同人群中报道了涉及一个或多个外显子的新型 CYP21A2 缺失。由于这些重排以前从未在 21-羟化酶缺乏症的遗传史中描述过，因此这些新的缺失引起了特别的关注。然而，这些新的重排可能是多重连接依赖性探针扩增（MLPA）的不正确解释的结果。
