Evidence map›Paper›PMID 39623453›Full record

ArticleOrphanet journal of rare diseases2024

Clinical spectrum and molecular basis in 19 Chinese patients with 46, XY disorder of sexual development caused by NR5A1 mutations.

Yue Xu, Xuemeng Liu, Yang Liu, Hui Zhu, Jing Wu, Bing Han, Shiying Ling, Ren Cao, Haijun Yao, Yan Chen and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Orphanet journal of rare diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Frontiers in endocrinology · 2026
    Article
  3. 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

16 authors.

Yue Xu *Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Xuemeng Liu *Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Yang Liu *Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Hui Zhu *Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Jing WuThe Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Bing HanDepartment of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Shiying LingDepartment of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Ren CaoDepartment of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Haijun YaoDepartment of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Yan ChenDepartment of Obstetrics and Gynecology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Yu LiuDepartment of Radiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Yamin RaoDepartment of Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Xiaoyu LiuThe Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Shuangxia ZhaoThe Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Huaidong SongThe Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. huaidong_s1966@163.com.
Jie QiaoDepartment of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China. qiaoj2001@126.com.ORCID 0000-0001-7623-432X

Funding

National Natural Science Foundation of China 81873652National Natural Science Foundation of China 82371873Rare Disease Registration of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine JYHJB202306
6 · The paper itself

Abstract

backgroundNuclear receptor subfamily 5 group A member 1 (NR5A1) plays pivotal roles in steroidogenesis and gonadal development. 46, XY disorder of sexual development (DSD) caused by NR5A1 mutations is a rare genetic condition. This study aimed to provide a comprehensive analysis of the clinical characteristics and molecular defects observed in 19 Chinese patients with NR5A1 variants, including assessing the deleterious effects of novel variants in vitro and evaluating their functional impact on the gonad and adrenal glands in vivo. MATERIALS AND

methodsSubjects with NR5A1 variants were identified from 223 Chinese 46, XY DSD patients via next-generation sequencing. In-silico analysis and functional assays were performed to evaluate the transcriptional activity, expression levels and nuclear localization of novel NR5A1 variants. The histological structure of the gonads was evaluated via immunohistochemistry (IHC).

resultsPatients with NR5A1 gene variants presented with serious conditions, including micropenis, cryptorchidism, azoospermia, and radiological abnormalities of the spleen. Five novel NR5A1 variants were identified, including heterozygous p.Y5*, p.Q42E and p.L359_L363del, as well as copy number variation (CNV) of chr9:127213317-127570245_del and an exon 6 duplication. A total of 63.2% (12/19) of patients harbored additional variants other than NR5A1. Defective transcriptional regulatory activities and abnormal protein expression levels were observed in NR5A1 variants. The reduced levels of DHEA-S and 11-oxygenated steroids indicate a mild impairment in adrenal function among certain patients. The IHC analysis of the testis revealed intact expression levels of SOX9 in Sertoli cells, while significant differences were observed in the expression pattern of CYP17A1 in Leydig cells among patients. The preserved maturation of adult Leydig cells in the patients may trigger spontaneous puberty.

conclusionsPatients with NR5A1 mutations exhibit complex phenotypes. The observed clinical heterogeneity may be attributed to oligogenic mutations, dysregulated Leydig cell function, as well as the impaired ability to modulate the transcription of target genes.

Indexed as

Disorder of Sex Development, 46,XYSteroidogenic Factor 1AdolescentAdultChildChild, PreschoolChinaEast Asian PeopleFemaleHumansInfantMaleMutationNR5A1 protein, humanSteroidogenic Factor 1Disorder/differences of sexual development (DSD)Genotype–phenotype correlationLeydig cell developmentNuclear receptor subfamily 5 group A member 1 (NR5A1) mutation

Identifiers

PMID39623453
PMCPMC11610102

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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.