Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China; Department of Clinical Psychology, School of Health in Social Science, The University of Edinburg, Edinburg, United Kingdom.
Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China; Center of Neonatal Disease Screening, Quanzhou Maternity and Children's Hospital, Quanzhou, China.
Eur J Med Genet. 2024 Jun;69:104950. doi: 10.1016/j.ejmg.2024.104950. Epub 2024 Jun 1.
Newborn screening (NBS) for congenital adrenal hyperplasia (CAH) based on hormonal testing is successfully implemented in many countries. However, this method cannot detect non-classic CAH and has high false positive rates. We have developed a novel MALDI-TOF MS assay that can identify common variants and deletions of CYP21A2 in the Chinese population. Thirty-seven clinical patients with CAH confirmed by Sanger sequencing and MLPA analysis were detected by MALDI-TOF MS assay. Two CYP21A2 variants were detected in 30 patients and one CYP21A2 variant was detected in 7 patients. The MALDI-TOF MS assay detected 67 mutant alleles in 37 patients with a detection rate of 90.5%. Sanger sequencing revealed that three variants in seven patients were not included in the designed panel. Eleven distinct CYP21A2 variants were identified, including five missense variants, two nonsense variants, two large gene deletions, one splice variant, and one frameshift variant. The most frequent variant was c.293-13C > G (37.84%), followed by c.518T > A (21.62%) and exon 1-7 deletion (17.57%). The high-throughput MALDI-TOF MS assay that can simultaneously detect common variants and deletions of CYP21A2. This assay can be used for population-based genetic screening and rapid detection of suspected patients, and is expected to be a valuable complement to biochemical-based testing for the detection of CAH.
新生儿筛查（NBS）基于激素检测已在许多国家成功实施，用于先天性肾上腺皮质增生症（CAH）。然而，这种方法不能检测非经典 CAH，并且假阳性率很高。我们开发了一种新的 MALDI-TOF MS 分析方法，可以鉴定中国人 CYP21A2 的常见变异和缺失。通过 MALDI-TOF MS 分析检测了 37 例经 Sanger 测序和 MLPA 分析证实的 CAH 临床患者。在 30 例患者中检测到两种 CYP21A2 变异，在 7 例患者中检测到一种 CYP21A2 变异。MALDI-TOF MS 分析在 37 例患者中检测到 67 个突变等位基因，检出率为 90.5%。Sanger 测序显示，7 例患者中的三种变异未包含在设计面板中。共鉴定出 11 种不同的 CYP21A2 变异，包括 5 种错义变异、2 种无义变异、2 种大片段基因缺失、1 种剪接变异和 1 种移码变异。最常见的变异是 c.293-13C>G（37.84%），其次是 c.518T>A（21.62%）和外显子 1-7 缺失（17.57%）。该高通量 MALDI-TOF MS 分析方法可以同时检测 CYP21A2 的常见变异和缺失。该检测方法可用于人群遗传筛查和疑似患者的快速检测，有望成为生化检测 CAH 的有益补充。
