Patjamontri S.Lucas-Herald A.K.McMillan M.Prasad R.Metherell L.A.McGowan R.Tobias E.S.Ahmed S.F.Mahidol University2024-06-032024-06-032023-01-01Hormone Research in Paediatrics (2023)16632818https://repository.li.mahidol.ac.th/handle/20.500.14594/98605Introduction: 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 boys 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.Biochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1159/0005355282-s2.0-851814949641663282638011841