Clinical Report: A Novel TXNRD2 Variant Linked to Familial Glucocorticoid Deficiency
Overview
This report identifies a novel homozygous TXNRD2 variant associated with familial glucocorticoid deficiency (FGD) in a Saudi patient. The findings expand the genetic understanding of FGD and highlight the role of mitochondrial dysfunction in adrenal insufficiency.
Background
Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by cortisol deficiency and elevated ACTH levels. Recent advances in genetics have revealed that FGD is a genetically heterogeneous condition, with various genes implicated in its pathogenesis. Understanding the genetic basis of FGD is crucial for accurate diagnosis and management of affected individuals.
Data Highlights
Variant
Type
Frequency
Effect
c.575C>T (p.Pro192Leu)
Homozygous
0.00000479
Likely pathogenic
Key Findings
A novel homozygous TXNRD2 variant (c.575C>T) was identified in a patient with FGD.
The variant was not found in a local population database of over 18,000 exomes.
The variant affects a highly conserved amino acid and is predicted to be deleterious.
No other pathogenic variants were found in known FGD-associated genes.
Clinical Implications
Clinicians should consider genetic testing for TXNRD2 variants in patients presenting with symptoms of adrenal insufficiency, particularly in cases of familial glucocorticoid deficiency. Early identification of such variants can inform management strategies and genetic counseling for affected families.
Conclusion
The identification of this novel TXNRD2 variant enhances the understanding of the genetic landscape of familial glucocorticoid deficiency and underscores the importance of mitochondrial function in adrenal health.
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
Researchers found that patients with higher waist circumference and lower grip strength had the greatest risk for developing type 2 diabetes during long-term follow-up.
