ORIGINAL RESEARCH article
Front. Pediatr.
Sec. Genetics of Common and Rare Diseases
Volume 13 - 2025 | doi: 10.3389/fped.2025.1585582
This article is part of the Research TopicInborn Errors of Redox Metabolism - An Emerging FieldView all articles
Case Report and Literature Review: Novel TXNRD2 Compound Heterozygous Variants in Familial Glucocorticoid Deficiency Type 5
Provisionally accepted
- Children's Hospital of Soochow University, Suzhou, China
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Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by isolated glucocorticoid deficiency. Mutations of MC2R, MRAP, STAR, NNT, and TXNRD2 have been implicated in FGD pathogenesis. To date, only four families with TXNRD2-associated familial Glucocorticoid Deficiency Type 5 (FGD5) have been reported worldwide. We report a patient with clinical features consistent with FGD5, increasing the total number of reported cases. Including this case, 11 probands across five independent kindreds have now been identified globally.Functional studies demonstrated that the novel compound heterozygous variants (c.1391A>G; p.H464R and c.1141C>T; p.R381W) reduce TXNRD2 protein levels in a heterologous expression system. This case expands the genetic spectrum of FGD5 and suggests a potential association between TXNRD2 variants and electrocardiographic abnormalities. Our findings underscore the importance of TXNRD2 in adrenal redox homeostasis and provide new insights for FGD5 diagnosis.
Keywords: FGD5, TXNRD2, exome sequencing, qPCR, Glucocorticoid deficiency
Received: 28 Feb 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Wang, Chen, chen, Xie, Chen, wu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: haiying wu, Children's Hospital of Soochow University, Suzhou, China
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