To identify and characterize a novel TXNRD2 variant associated with familial glucocorticoid deficiency (FGD) in a Saudi family, enhancing understanding of the genetic basis of this condition.
Key Findings:
A novel missense homozygous TXNRD2 variant (c.575C>T (p.Pro192Leu)) was identified in the proband, suggesting a significant genetic contribution to FGD.
The variant was found in a heterozygous state in both parents, supporting autosomal recessive inheritance.
The variant is extremely rare, with a minor allele frequency of 0.00000479 in international population databases, indicating its potential pathogenicity.
In silico tools predicted the variant to have deleterious effects on protein structure and function, which may contribute to the clinical presentation of FGD.
Interpretation:
The findings expand the genetic spectrum of TXNRD2-associated FGD and suggest that mitochondrial redox dysregulation may play a critical role in the pathophysiology of adrenal insufficiency.
Limitations:
The study is based on a single case, limiting the generalizability of the findings to broader populations.
No pathogenic variants were found in other known FGD-associated genes, which may suggest a need for further investigation into other genetic factors.
Conclusion:
This report adds a novel TXNRD2 variant to the limited cases of FGD, enhancing understanding of the genetic basis of this condition and its implications for mitochondrial function.
by Ibrahim Al Alwan, Kheloud M. Alhamoudi, Abdullah Ibrahim Alzaben, Beshaier Almulhem, Nawal Qawasmi, Meshael Alswailem, Sara Alotaibi, Burair Alsaihati, Amjad Jabaan, Moeber Mahzari, Christa E. Flück, Ali S. Alzahrani
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