Evidence map›Paper›PMID 42551237›Full record

ArticleEBioMedicine2026

Establishing the role of ZBTB20 mutations in GnRH deficiency and impaired neurogenesis in the subventricular zone: a human cohort and animal model study.

Jun Guan, Jingtan Zhu, Yuting Li, Min Nie, Jing Zhang, Zhiheng Chen, Huadie Liu, Dan-Na Chen, Ruizhi Zheng, Meichao Men and 1 more

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Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

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4 · The record

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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

11 authors.

Jun GuanFurong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, PR China; Hunan Key Laboratory of Animal Models for Human Diseases, Changsha, Hunan 410078, PR China; Hunan Key Laboratory of Medical Genetics, Changsha, Hunan 410078, PR China; Medical Genetic Center, Jiangxi Maternal and Child Health Hospital, No 318, Bayi Avenue, Nanchang, China.
Jingtan ZhuFurong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, PR China; Hunan Key Laboratory of Animal Models for Human Diseases, Changsha, Hunan 410078, PR China; Hunan Key Laboratory of Medical Genetics, Changsha, Hunan 410078, PR China.
Yuting LiDepartment of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Min NieNHC Key Laboratory of Endocrinology, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Jing ZhangHunan Key Laboratory of Medical Genetics, Changsha, Hunan 410078, PR China; Department of Laboratory Animals, Central South University, Changsha, Hunan 410078, China.
Zhiheng ChenDepartment of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Huadie LiuMOE Key Laboratory of Rare Pediatric Diseases, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China.
Dan-Na ChenDepartment of Basic Medical Sciences, Changsha Medical University, Changsha, Hunan 410219, China.
Ruizhi ZhengDepartment of Endocrinology, The People's Hospital of Henan Province, Zhengzhou, Henan 450003, China.
Meichao MenDepartment of Clinical Nutrition, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China. Electronic address: menmeichao@csu.edu.cn.
Jia-Da LiFurong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, PR China; Hunan Key Laboratory of Animal Models for Human Diseases, Changsha, Hunan 410078, PR China; Hunan Key Laboratory of Medical Genetics, Changsha, Hunan 410078, PR China. Electronic address: lijiada@sklmg.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCongenital hypogonadotropic hypogonadism (CHH) arises from defective development or dysfunction of GnRH neurons. Olfactory bulb (OB) malformations frequently accompany CHH, a condition termed Kallmann syndrome (KS). Nevertheless, approximately 50% of CHH cases remain genetically undefined.

methodsLeveraging our 15-year effort in building one of Asia's largest CHH cohorts (812 unrelated patients, and 49 CHH families), we identified a pathogenic ZBTB20 mutation (p.R300C) in a four-generation CHH family with seven affected members. We generated nervous system-specific Zbtb20 conditional knockout (cKO) mice to assess phenotypic and mechanistic consequences. Molecular analyses, including transcriptional regulation assays, were performed to explore downstream pathways.

findingsFour additional heterozygous ZBTB20 variants were detected in the CHH cohort. Zbtb20 cKO mice recapitulated hallmark CHH features: GnRH neuron deficiency, hypogonadism, and infertility. Notably, migration of GnRH neurons in Zbtb20-deficient embryos was stalled along the defective terminal nerve (TN) scaffold. Furthermore, Zbtb20 deficiency impaired proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) and disrupted their migration via the rostral migratory stream (RMS) to the OB. We also identified Thbs4 as a key downstream target, as ZBTB20 transcriptionally activates Thbs4, which is critical for SVZ NSCs migration.

interpretationOur study establishes ZBTB20 as a CHH-associated gene and demonstrates its essential role in SVZ-OB neurogenesis. Loss of ZBTB20 function leads to OB atrophy, disrupted terminal nerves, GnRH deficiency and CHH pathogenesis.

fundingThis project is financially supported by National Natural Science Foundation of China, and the Natural Science Foundation of Hunan Province.

Indexed as

Congenital hypogonadotropic hypogonadismGeneticsKallmann syndromeZBTB20

Identifiers

PMID42551237
PMCPMC13470097

What Socratic holds

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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 Socratic graph.