Journal of Shanghai Jiao Tong University (Medical Science) ›› 2022, Vol. 42 ›› Issue (5): 557-561.doi: 10.3969/j.issn.1674-8115.2022.05.001

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Molecular diagnosis and clinical significance of 21-hydroxylase deficiency

LÜ Yongfen(), LI Pin()   

  1. 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;
  • Supported by:
    National Natural Science Foundation of China(81871131)


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

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