Case report and literature review: novel TXNRD2 compound heterozygous variants in familial glucocorticoid deficiency type 5
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 Def...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2025.1585582/full |
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| author | Xiaoyan Wang Xiuli Chen Ting Chen Rongrong Xie Qi Lin Chen Haiying Wu Fengyun Wang |
| author_facet | Xiaoyan Wang Xiuli Chen Ting Chen Rongrong Xie Qi Lin Chen Haiying Wu Fengyun Wang |
| author_sort | Xiaoyan Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2b24ccf60901491db85e6ec02f81ca54 |
| institution | Kabale University |
| issn | 2296-2360 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj-art-2b24ccf60901491db85e6ec02f81ca542025-08-20T03:49:56ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602025-07-011310.3389/fped.2025.15855821585582Case report and literature review: novel TXNRD2 compound heterozygous variants in familial glucocorticoid deficiency type 5Xiaoyan WangXiuli ChenTing ChenRongrong XieQi Lin ChenHaiying WuFengyun WangFamilial 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.https://www.frontiersin.org/articles/10.3389/fped.2025.1585582/fullFGD5TXNRD2exome sequencingqPCRglucocorticoid deficiency |
| spellingShingle | Xiaoyan Wang Xiuli Chen Ting Chen Rongrong Xie Qi Lin Chen Haiying Wu Fengyun Wang Case report and literature review: novel TXNRD2 compound heterozygous variants in familial glucocorticoid deficiency type 5 Frontiers in Pediatrics FGD5 TXNRD2 exome sequencing qPCR glucocorticoid deficiency |
| title | Case report and literature review: novel TXNRD2 compound heterozygous variants in familial glucocorticoid deficiency type 5 |
| title_full | Case report and literature review: novel TXNRD2 compound heterozygous variants in familial glucocorticoid deficiency type 5 |
| title_fullStr | Case report and literature review: novel TXNRD2 compound heterozygous variants in familial glucocorticoid deficiency type 5 |
| title_full_unstemmed | Case report and literature review: novel TXNRD2 compound heterozygous variants in familial glucocorticoid deficiency type 5 |
| title_short | Case report and literature review: novel TXNRD2 compound heterozygous variants in familial glucocorticoid deficiency type 5 |
| title_sort | case report and literature review novel txnrd2 compound heterozygous variants in familial glucocorticoid deficiency type 5 |
| topic | FGD5 TXNRD2 exome sequencing qPCR glucocorticoid deficiency |
| url | https://www.frontiersin.org/articles/10.3389/fped.2025.1585582/full |
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