| Autor: |
Patjamontri, Supitcha, Lucas-Herald, Angela K., McMillan, Martin, Prasad, Rathi, Metherell, Louise A., McGowan, Ruth, Tobias, Edward S., Ahmed, S. Faisal |
| Předmět: |
|
| Zdroj: |
Hormone Research in Paediatrics; 2024, Vol. 97 Issue 5, p509-514, 6p |
| Abstrakt: |
Introduction: Variants in genes that play a role in maintaining cellular redox homeostasis in adrenocortical cells may be associated with glucocorticoid deficiency, and it is unclear whether these cases may be associated with a wider phenotype. However, to date, only 1 case of a genetic variant in thioredoxin reductase type 2 (TXNRD2) in a South Asian kindred with familial glucocorticoid deficiency has been reported. Case Presentation: The index case was diagnosed with selective glucocorticoid deficiency at 10 years of age. He had a history of a small penis and a right undescended testis, which subsequently required an orchidopexy. The parents were of Pakistani origin and first cousins. The boy's gonadal function was normal and autosomal recessive missense homozygous variants p.Val361Met;Val361Met in TXNRD2 were identified in him by whole-genome sequencing. Functional studies were performed using peripheral blood mononuclear cells from the patient, unaffected parents, and four age-matched healthy boys. Compared to the carriers and controls, the case had lower TXNRD2 protein on immunoblotting using anti-TXNRD2 antibody (1.3-fold), 95% CI: 1.8 (1.5–2.1), lower mRNA expression of TXNRD2 on quantitative RT-PCR (1.6-fold), 95% CI: 1.1 (0.7–1.4), and a lower glutathione:oxidized glutathione ratio (6.7-fold), 95% CI: 2.0 (1.6–2.4). Conclusions: In addition to confirming the critical role that TXNRD2 serves in maintaining adrenal function, by reporting the findings of atypical genitalia, this case further extends the phenotype. Established Facts: Nicotinamide nucleotide transhydrogenase (NNT) and TXNRD2 genes play a role in maintaining cellular redox homeostasis in adrenocortical cells and have been identified as genetic causes of glucocorticoid deficiency with or without mineralocorticoid deficiency. To date, a single report of familial glucocorticoid deficiency in a South Asian kindred has been described to be associated with a genetic variant in TXNRD2. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
