PMC9989011_01
Pedigree of a family with autosomal dominant mutation in the C-terminal sequence of the TREX1 gene (pVAL235Glyfs*6) leading to RVCLS.
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F1
Under the hypothesis:later turned out to be incorrect:of a pathological accumulation of intracellular retroviral elements due to an impaired function of the exonuclease activity of TREX1, we treated this index patient with a combination of anti-retroviral drugs (emtricitabine, tenofovir, nevirapine) (Figure 1, Supplementary material case synopsis and Supplementary Table S2). Figures S1A, B) and contrast-enhancing lesions particularly in the cerebellum (Supplementary Figure S1C). This lesion burden showed a slower increase under ruxolitinib treatment. Further deterioration of visual acuity of the index patient was stopped and even improved in the left eye from 0.05 to 0.2 and also microbleeds were reduced.
Time course of CXCL10 mRNA transcript expression in PBMCs of the index patient and eight age- and sex-matched healthy controls (Top) and body weight of the index patient (Bottom). RT-PCR results were normalized to TATA-binding-protein (Top). Anti-retroviral treatment: Emtricitabine (200 mg per day), Tenofovir disoproxil fumarate (245 mg per day), Nevirapine (400 mg per day) and JAK inhibitor treatment: Ruxolitinib (10-25 mg per day). *In 09/2014 the patient was not taking any immunosuppressive drugs.
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F2
Indeed, in the index patient we observed elevated antinuclear autoantibodies (ANA), together with elevated CXCL10 transcripts in PBMCs at several time points (Supplementary Table S3, Figure 2). In parallel, we found a persistent drop in CXCL10 transcripts, ANA titers decreased and body weight stabilized (Figure 2).