Oakley, Julia, Hill, Martin, Giess, Adam et al. · Journal of translational medicine · 2023 · DOI
Researchers used advanced DNA sequencing technology to find a structural variant (a large rearrangement in genetic material) in the AKR1C gene region of a patient with severe, unexplained fatigue. This variant appears to alter how the body produces certain steroids and neurochemicals, potentially leading to reduced neuronal activity and widespread tissue dysfunction. The discovery suggests that genetic changes in this region may be a cause of severe chronic fatigue in some patients, and blood tests for specific steroid markers could help identify others with similar underlying issues.
This study demonstrates that structural variants in complex genomic regions may account for previously undiagnosed cases of ME/CFS, particularly in patients with severe, treatment-resistant fatigue. The identification of specific steroid biomarkers provides a potential diagnostic tool to identify a patient subgroup that might benefit from targeted treatments. Understanding the mechanistic link between genetic variation and neurosteroid dysregulation opens new research and therapeutic directions for ME/CFS.
This single case study does not prove that AKR1C variants cause ME/CFS in the general patient population, nor does it establish the prevalence of this variant among ME/CFS patients. The study cannot determine whether the observed steroid abnormalities are causative of fatigue or merely associated, and findings from one patient may not generalize to other patients with ME/CFS. Further validation in larger, prospective cohorts is required before any diagnostic or therapeutic claims can be substantiated.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
Contribute
Private, reviewed by a human. Not a public comment thread.