7 of the 8 patients presenting with negative IS were positive in mutations of RNASEH2B and 98% of patients with mutations in other AGS related genes had positive IS. Additionally, a lower morbidity and mortality rate is associated with RNASEH2B positive patients compared to the other tested genotypes. 

Tulane University

The discussion section of the study assessing interferon-related biomarkers in Aicardi-Goutières syndrome (AGS) focuses on interferon-stimulated gene (ISG) expression and type I IFN signaling, the implications of mutations in relevant genes (such as TREX1, RNASEH2, SAMHD1, ADAR, and RNASEH2B), and the correlation between the interferon score and patient age.

Discussion of Interferon Biomarker Assessment in AGS

Rice GI, Forte GM, Szynkiewicz M, Chase DS, Aeby A, Abdel-Hamid MS, Ackroyd S, Allcock R, Bailey KM, Balottin U, Barnerias C, Bernard G, Bodemer C, Botella MP, Cereda C, Chandler KE, Dabydeen L, Dale RC, De Laet C, De Goede CG, Del Toro M, Effat L, Enamorado NN, Fazzi E, Gener B, Haldre M, Lin JP, Livingston JH, Lourenco CM, Marques W Jr, Oades P, Peterson P, Rasmussen M, Roubertie A, Schmidt JL, Shalev SA, Simon R, Spiegel R, Swoboda KJ, Temtamy SA, Vassallo G, Vilain CN, Vogt J, Wermenbol V, Whitehouse WP, Soler D, Olivieri I, Orcesi S, Aglan MS, Zaki MS, Abdel-Salam GM, Vanderver A, Kisand K, Rozenberg F, Lebon P, Crow YJ. Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol. 2013 Dec;12(12):1159-69. doi: 10.1016/S1474-4422(13)70258-8. Epub 2013 Oct 30. PMID: 24183309; PMCID: PMC4349523.

Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study

Type I IFN is produced by cells in response to an intracellular viral infection, blocking reinfection of the virus. Multiple forms of IFN exist, evidenced by the 17 genes located on chromosome 9p. A significant factor of the cellular antiviral response induced by type I IFN, is the expression of interferon stimulated genes (ISGs). A multitude of ISGs have been identified and their relation to interferon signatures has been published numerous times. However, there is little information about the genes products of ISGs and their antiviral properties, signaling cascades and specificity. 

ISG Expression & Type I IFN Signaling

Patients with mutations in one of these genes referenced produced a reportable type I IFN signature, suggesting a strong relationship between these genotypes and IFN. 

Mutations in TREX1, RNASEH2, SAMHD1 and ADAR

Mutations in RNASEH2B

- Correlation between IFN score and age
- Repeat Testing Yields Similar Results

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