Wang Xudong, Lu Xingxiu, Zheng Faming, Lin Kun, Liao Minjuan, Dong Yi, Chen Tiantian, He Ying, Lu Mei, Chen Jing, Li Yanfang, Zhou Yulin
Xiamen Newborn Screening Center, Department of Pediatrics, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen 361102, China.
United Diagnostic and Research Center for Clinical Genetics, School of Public Health, Xiamen University, Xiamen 361100, China.
Int J Neonatal Screen. 2025 Mar 13;11(1):22. doi: 10.3390/ijns11010022.
Long-read sequencing (LRS) provides comprehensive genetic information, but research of LRS applied to congenital adrenal hyperplasia (CAH) newborn screening is limited. This study aimed to evaluate the clinical utility of LRS in genetic diagnosis and second-tier newborn screening. Neonates born between January 2017 and December 2022 in Fujian, China, were recruited for biochemical and LRS-based genetic screening assay. The LRS covers the entire gene regions and exon-intron boundary regions for , , , , and . In this retrospective study, 1,774,555 newborns received 17α-OHP screening, yielding a screening positive rate of 0.20%. Of these high-risk neonates, 3411 were successfully recalled for re-evaluation. Finally, 66 neonates were diagnosed with CAH, with a positive predictive value of 28.82%. Based on this data, the overall prevalence of CAH in Fujian was estimated to be 1:26,883. LRS was performed on 57 neonates with 21-hydroxylase deficiency (21-OHD) and 109 variant alleles were identified. The c.293-13C>G variant (31.19%) was the most prevalent in Fujian. Additionally, 647 neonates with suspected positive results were genotyped, and 41 were identified as carriers, with carrier frequencies of 1:18 for , 1:162 for , and 1:324 for in Xiamen. Therefore, LRS can provide comprehensive genotypes in approximately 1.5 days at a cost of less than $20 USD per sample, and effectively improve screening efficiency, reduce anxiety of parents during newborn screening (NBS), and shorten the time to referral of CAH patients (approximately 10 days). Such a combined screening strategy is worthy to be recommended for NBS programs in the future.
长读长测序（LRS）可提供全面的遗传信息，但将LRS应用于先天性肾上腺皮质增生症（CAH）新生儿筛查的研究有限。本研究旨在评估LRS在基因诊断和二级新生儿筛查中的临床应用价值。招募了2017年1月至2022年12月在中国福建出生的新生儿进行生化和基于LRS的基因筛查检测。LRS覆盖了 、 、 、 及 的整个基因区域和外显子 - 内含子边界区域。在这项回顾性研究中，1,774,555名新生儿接受了17α - 羟孕酮（17α - OHP）筛查，筛查阳性率为0.20%。在这些高危新生儿中，3411名被成功召回进行重新评估。最终，66名新生儿被诊断为CAH，阳性预测值为28.82%。基于此数据，福建CAH的总体患病率估计为1:26,883。对57名21 - 羟化酶缺乏症（21 - OHD）新生儿进行了LRS检测，共鉴定出109个变异等位基因。c.293 - 13C>G变异（31.19%）在福建最为常见。此外，对647名疑似阳性结果的新生儿进行了基因分型，其中41名被鉴定为携带者，厦门地区 、 、 的携带者频率分别为1:18、1:162和1:324。因此，LRS能够在约1.5天内提供全面的基因型，每个样本成本低于20美元，有效提高筛查效率，减少新生儿筛查（NBS）期间家长的焦虑，并缩短CAH患者的转诊时间（约10天）。这种联合筛查策略值得未来推荐用于NBS项目。
