Assessment of Long-Read Sequencing-Based Congenital Adrenal Hyperplasia Genotyping Assay for Newborns in Fujian, China
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Newborn screening for congenital adrenal hyperplasia is mainly based on determination of 17-hydroxyprogesterone in dried blood spots samples. Long-read sequencing enables to provide comprehensive genetic information, but it has not been applied in second-tier screening and molecular diagnosis of NBS program.Method: This retrospective study included 6 newborn screening centers in Fujian, China. Participants were neonates born between January 2017 and December 2022. All neonates received bio-chemical screening assay, and long-read sequencing-based CAH genotyping assay was performed in CAH patients from Fujian and neonates with screening-positive values from Xiamen.Findings: In this retrospective study, 1,774,555 newborns received bio-chemical screening assay, yielding a screening positive rate of 0.20%. Of these high-risk neonates, 3,411 (94.25%) were successfully recalled for re-evaluation. Finally, 67 neonates were diagnosed with CAH, indicating the positive predictive value was 29.26%. Based on these data, the overall prevalence of CAH in Fujian Province was estimated to be 1:26,486. Long-read sequencing was performed in 58 neonates with 21-OHD, which identified 109 variant alleles. Among these variants, c.293-13C>G (31.19%) is the most prevalent variation in Fujian population. Additionally, 647 neonates with suspicious positive results were genotyped and totally 41 neonates were identified as carriers, with a carrier frequency of 1:18 in CYP21A2 (1:65 in classic variants, and 1:26 in non-classic variants), 1:162 in HSD3B2, and 1:324 in CYP17A1 in Xiamen.Interpretation: Long-read sequencing can effectively improve screening efficiency, and reduce anxiety during newborn screening. Therefore, such combined screening strategy is worthy to be recommended for newborn screening program.
DOI: 10.3390/ijns11010022
Authors: Xudong Wang, Xingxiu Lu, Faming Zheng, Kun Lin, Minjuan Liao, Yi Dong, Tiantian Chen, Ying He, Mei Lu, Jing Chen, Yanfang Li, Aiping Mao, Yulin Zhou
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,930
OpenAlex ID: W4408409007