Evidence map›Paper›PMID 41469707›Full record

ArticleGenome medicine2025

Genetic characterization and screening of congenital adrenal hyperplasia by long-read sequencing in a cohort of 21,239 newborns.

Desheng Liang, Min Zhu, Qiaowei Liang, Rong Qiang, Lei Yu, Shiyi Xu, Menglin Li, Jieping Song, Yulin Zhou, Xiaoyan He and 23 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Short-Read NGS of a Long-RangeInternational journal of molecular sciences · 2026
    Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

33 authors.

Desheng Liang *Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, MOE KeyLab of Rare Pediatric Diseases, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China. liangdesheng@sklmg.edu.cn.
Min Zhu *Department of Endocrinology and Genetic Metabolic Diseases, National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400013, China.
Qiaowei Liang *Department of Medical Genetics, Hunan Jiahui Genetics Hospital, Changsha, Hunan, 410078, China.
Rong Qiang *Center of Neonatal Disease Screening, Department of Clinical Genetics, Northwest Women's and Children's Hospital, Xi'an, 710061, China.
Lei Yu *Prenatal Diagnosis Center, Guiyang Maternal and Child Health Care Hospital, Guiyang, Guizhou, 550001, China.
Shiyi Xu *Department of Endocrinology and Inborn Metabolic Diseases, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fuzhou, Fujian, 350014, China.
Menglin LiCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, MOE KeyLab of Rare Pediatric Diseases, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
Jieping SongMedical Genetics Center, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei, 430070, China.
Yulin ZhouUnited Diagnostic and Research Center for Clinical Genetics, Women and Children's Hospital, School of Medicine and School of Public Health, Xiamen University, Xiamen, 361102, China.
Xiaoyan HeClinical Molecular Medicine Center, Children's Hospital, Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, China.
Yonglan HuangGuangzhou Newborn Screening Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510180, China.
Hua JinDepartment of Prenatal Diagnosis, Jinan Maternal and Child Health Hospital, Jinan, Shandong, 250001, China.
Jianqiang TanLiuzhou Maternity and Child Healthcare Hospital, Liuzhou, Guangxi, 545000, China.
Hui LiuDepartment of Endocrinology and Inborn Metabolic Diseases, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fuzhou, Fujian, 350014, China.
Aihua XiaDepartment of Obstetrics, Beihai People's Hospital, Beihai, Guangxi, 536000, China.
Yingdi LiuCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, MOE KeyLab of Rare Pediatric Diseases, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
Peisen LiuCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, MOE KeyLab of Rare Pediatric Diseases, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
Zhuo LiCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, MOE KeyLab of Rare Pediatric Diseases, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
Ruifang WangDepartment of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China.
Dongjuan WangClinical Molecular Medicine Center, Children's Hospital, Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, China.
Ruixue ZhangCenter of Neonatal Disease Screening, Department of Clinical Genetics, Northwest Women's and Children's Hospital, Xi'an, 710061, China.
Qian PuPrenatal Diagnosis Center, Guiyang Maternal and Child Health Care Hospital, Guiyang, Guizhou, 550001, China.
Jinfu ZhouMedical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, China.
Runhong XuMedical Genetics Center, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei, 430070, China.
Xudong WangXiamen Newborn Screening Center, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
Minyi TanGuangzhou Newborn Screening Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510180, China.
Dayu ChenLiuzhou Maternity and Child Healthcare Hospital, Liuzhou, Guangxi, 545000, China.
Chaoyan WuDepartment of Obstetrics, Beihai People's Hospital, Beihai, Guangxi, 536000, China.
Di CuiDepartment of Research and Development, Berry Genomics Corporation, Beijing, 102200, China.
Aiping MaoDepartment of Research and Development, Berry Genomics Corporation, Beijing, 102200, China. maoaiping@berrygenomics.com.
Wenhao ZhouDivision of Neonatology and Center for Newborn Care, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China. zhouwenhao@fudan.edu.cn.
Wenjuan QiuDepartment of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China. qiuwenjuan@xinhuamed.com.cn.
Lingqian WuCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, MOE KeyLab of Rare Pediatric Diseases, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China. wulingqian@sklmg.edu.cn.

Funding

Clinical Innovation Project and Academic Climbing Project of Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University 23XHCR12B, XKPF2024A100, XKPF2024B100Foundation for Innovative Research Groups of the National Natural Science Foundation of China 81770200Shanghai Healthcare Commission Project 202340103The National Key R&D Program of China 2022YFC2703400The National Key R&D Program of China 2022YFC2703700
6 · The paper itself

Abstract

backgroundComprehensive genetic characterization and screening for congenital adrenal hyperplasia (CAH) have not yet been achieved at the population level because of the complexity of the CYP21A2 locus. This prospective study incorporated long-read sequencing (LRS) into the current first-tier biochemical newborn screening (NBS) to comprehensively characterize the variant spectrum of CYP21A2, fully investigate the carrier frequency and expected incidence of classic and non-classic CAH (NCCAH), and evaluate the clinical feasibility of genetic NBS for CAH.

methodsA total of 21,239 newborns were consecutively recruited from 11 centers across China between June 2023 and May 2024. All the participants underwent biochemical and genetic NBS. In vitro enzymatic activity and minigene assays were performed to determine the pathogenicity of novel variants. A 30.8-kb long amplicon, followed by LRS, was performed to determine the phasing of duplication chimera and single-nucleotide variations (SNVs) and indels in CYP21A2.

resultsEligible genetic screening results were obtained for 21,234 (99.98%) newborns. The allele frequencies of duplications and deletions at the CYP21A2 locus were 4.51% and 0.15%, respectively. In vitro functional analysis and LRS-based phasing were performed to precisely determine carrier alleles, setting an overall frequency of 1.67% (711/42468, 95% confidence interval (CI): 1.55–1.80%), with 0.75% (320/424268, 95% CI: 0.67–0.84%) and 0.92% (391/42468, 95% CI: 0.83–1.01%) for classic and NC carriers, respectively. Notably, hotspot variants including SNVs/indels caused by microgene conversion and 30-kb deletions caused by unequal crossover accounted for 84.0% (597/711), whereas rare variants comprised as high as 16.0% (114/711) of all variants. The expected incidence of classic CAH according to allele frequency was 1/17613. The expected incidence of NCCAH in Chinese population (1/4474) was significantly lower than that in US Ashkenazi Jews (1/133) and Caucasians (1/337), mainly owing to the different allele frequencies of the NC variant CYP21A2:c.844G > T. Biochemical NBS identified 106 (0.50%) positive samples with a positive predictive value of 0.94% (1/106). LRS accurately identified the one case of classic CAH, with no false positives.

conclusionsOur findings provide a population-level carrier frequency and incidence estimates with a comprehensive landscape of the CYP21A2 locus, and demonstrate the effectiveness of first-tier LRS-based genetic NBS for CAH.

Indexed as

Adrenal Hyperplasia, CongenitalGenetic TestingNeonatal ScreeningSteroid 21-HydroxylaseAllelesChinaFemaleGene FrequencyHumansInfant, NewbornMalePolymorphism, Single NucleotideProspective StudiesCYP21A2 protein, humanSteroid 21-HydroxylaseCarrier frequencyCongenital adrenal hyperplasiaCYP21A2Disease incidenceLong-read sequencingNewborn screening

Identifiers

PMID41469707
PMCPMC12866592

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.