Journal of Developmental Medicine(Electronic Version)  2025, Vol. 13 Issue (5): 330-337 DOI: 10.3969/j.issn.2095-5340.2025.05.002 |
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| Analysis of genetic screening results for monogenic diseases in newborns and exploration of screening strategies |
| Zeng Wen, Qi Hong , Zhu Jianjiang，et al
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(1. Department of Prenatal Diagnosis, Haidian District Maternal and Child Health Care Hospital, Beijing 100094, China;
2. Department of Neonatology, Haidian District Maternal and Child Health Care Hospital, Beijing 100094, China)
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Abstract 【Abstract】 Objective To analyze the results of genetic screening for monogenic disorders, investigate the characteristics of pathogenic genetic variants in the local population, and formulate a locally tailored newborn genetic screening strategy. Method A total of 2 217 newborns deliveredat the Haidian District Maternal and Child Health Care Hospital in Beijingbetween July 2022 and December 2024, whose guardians provided informed consent and voluntary request for genetic testing were enrolled. Targeted gene capture-based next-generation sequencing (NGS) was performed to screen
599 genes associated with 542 disease subtypes. Initial screen-positive individuals underwent familial verification using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), longrange polymerase chain reaction (LR-PCR), and other techniques. Result Among the 2 217 newborns, 716 cases (32.30%) were identified as positive through familial verification. This included 307 cases (13.85%) with UGT1A1 variants and 274 cases (12.36%) with FLG variants. After applying an adjusted classification strategy, cases with milder symptoms and favorable prognosis associated with UGT1A1 or FLG variants were reclassified as carriers and excluded from the positive case count. After re-analysis, 146 cases (6.59%)
were positive, 1 787 cases (80.60%) were recessive gene carriers, and 284 cases (12.81%) with no variants detected. Among the positive cases, there were 91 cases of autosomal dominant pathogenic variants, 7 cases of autosomal recessive homozygous variants, 31 cases of compound heterozygous variants, 8 cases of X-linked dominant heterozygous variants, 3 cases of X-linked recessive hemizygous variants, and 5 cases of mitochondrial gene variants. The top five genes by positive rate were FLG (0.50%), LDLR (0.50%), APOB (0.32%), GJB2 (0.27%), and G6PD (0.27%). Six positive cases exhibited clinical phenotypes during the neonatal period. The top ten genes in terms of carrier rates were UGT1A1 (49.35%), FLG (12.36%),
GJB2 (10.10%), CFTR (6.54%), DUOX2 (5.41%), ATP7B (3.47%), CYP21A2 (3.07%), SLC26A4 (2.98%), PAH(2.93%), and GALC (2.80%). Conclusion NGS based neonatal genetic screening enhances the ability to detect monogenic diseases in newborns. Combined with familial validation, it provides actionable guidance for early identification and intervention. Continuous refinement of strategies for neonatal genetic screening through data accumulation will enable more precise and efficient screening
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Received: 12 June 2025
Published: 01 October 2025
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