Evidence map›Paper›PMID 39776042›Full record

ArticleEndocrine2025

Functional study of three cases with novel TBX19 variants.

NokI Lei, Xiang Qiu, Wunying Li, Yanlin Liu, Ronggui Hu, Chuanyin Li, Wenli Lu

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrine, 2025. 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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0citing papers in PubMed
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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

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3 · Its place in the literature

Who cites it

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

NokI Lei *Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
Xiang Qiu *School of Medicine, Guizhou University, Guiyang, Guizhou, China.
Wunying Li *Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
Yanlin Liu *State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Ronggui HuState Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Chuanyin LiState Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. lichuanyin2013@sibcb.ac.cn.
Wenli LuDepartment of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China. lwl11146@rjh.com.cn.

Funding

National Natural Science Foundation of China 31900804Shanghai Science & Technology Committee 14411958600Shanghai Talent Development Fund 2017120
6 · The paper itself

Abstract

purposeCongenital isolated adrenocorticotropic hormone deficiency (CIAD) is an autosomal recessive disorder. This study identifies novel TBX19 variants for CIAD patients, explores its possible effect mechanism at the structural, functional and protein levels, and guides clinicians better understand the condition.

methodsThe clinical characteristics of three CIAD children were summarized. Multiple sequence alignment was performed and five algorithms, PROVEA, PolyPhen2, Mutation Taster, FATHMM, and I Mutant2.0, were used for the pathogenicity prediction. In addition, the three-dimensional protein structure of wild-type TBX19 was generated by Alphafold 3 and its variants were shown using PyMOL. Furthermore, immunoblotting analysis was applied to examine changes in the protein levels and the luciferase reporter assay was performed to further investigate the effects of TBX19 and its variants on pro-opiomelanocortin (POMC) transcriptional activity.

resultsWe describe three Chinese patients with CIAD caused by TBX19 variants. The TBX19 variant, c.856C>T (p.R286*) was classified as pathogenic according to ACMG, whereas the other four variants, c.377C>T (p.P126L), c.602A>T (p.E201V), c.401A>G (p.H134R) and c.299G>A (p.R100H) were predicted to be disease-causing. Variants lead to alter interactions, conformational changes in proteins or truncate protein. TBX19 and PITX1 cooperated, resulting in a strong synergistic activation effect on POMC transcriptional expression. A functional study showed that the variants in our study result in a significant suppression of POMC transcriptional activity compared to wild-type TBX19.

conclusionsOur study identifies five TBX19 loss-of-function variants, two of which are novel and that provides new perspectives into the pathophysiological mechanism and expands the variant spectrum in IAD.

Indexed as

T-Box Domain ProteinsChildHomeodomain ProteinsHumansMutationPro-OpiomelanocortinHomeodomain ProteinsPro-OpiomelanocortinT-Box Domain ProteinsTBX19 protein, humanCongenital isolated adrenocorticotropic hormone deficiencyPITX1POMCTBX19

Identifiers

PMID39776042
PMCPMC11933146

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