Nationwide carrier screening for congenital adrenal hyperplasia: integrated approach of CYP21A2 pathogenic variant genotyping and comprehensive large gene deletion analysis.
Level 4 - case-series / case-control
Cross-sectional cohort screening study (diagnostic/screening validation in a single group)
PubMed 39856693 · doi:10.1186/s12920-025-02089-5
What was done
Evaluation of an integrated molecular screening strategy for 21-hydroxylase deficiency (CYP21A2) congenital adrenal hyperplasia in 204 unrelated preconception individuals. The workflow combined Amplification-Refractory Mutation System (ARMS) PCR and mass spectrometry (MS) genotyping for nine prevalent pathogenic variants, alongside quantitative real-time PCR (qPCR) and PCR-based restriction fragment length polymorphism (PCR-based RFLP) for large gene deletion and conversion analysis.
What was found
The methods showed concordance between ARMS-PCR and MS genotyping, and between qPCR and PCR-based RFLP. Two individuals carried large-scale gene deletions, and one carried a minor-scale gene conversion. The estimated carrier frequency in this cohort was approximately 1 in 65 individuals.
Why it matters
Demonstrates a combined testing approach capable of capturing both point mutations and structural rearrangements in CYP21A2 for carrier screening programs.
Limits
The sample size was modest (n = 204). The panel targeted only nine common pathogenic variants, leaving rare variants undetected. Sensitivity, specificity, and exact concordance percentages were not numerically specified in the abstract.
Cited by
- partial The carrier frequency for congenital adrenal hyperplasia genetic mutations is approximately 1 in 12.