title: Illumina HiSeq 4000 paired end sequencing; Reverse transcriptase inhibitors in Aicardi-Goutières syndrome
design: Reverse transcriptase inhibitors in Aicardi-Goutières syndrome
library_construction_protocol: Whole blood was collected into PAXgene tubes (Qiagen, Valencia, CA). All evaluations and sampling were undertaken at the Clinical Investigation Centre, Institut Imagine, Hôpital Necker, Paris, France, with visits at Day 0 (D0), and then at 1 (M1), 3 (M3), 6 (M6), 9 (M9), 12 (M12) and 18 (M18) months thereafter. Treatment was initiated on D0 and stopped at M12. Routine bloods, vital signs, weight and height measurements were recorded at every visit. The study was registered with ClinicalTrials.gov (NCT02363452), sponsored by Assistance Publique – Hôpitaux de Paris (AP-HP: P140203 / EUDRACT 2014-002710-23) and the protocol approved by the Agence Nationale de Sécurité du médicament et des produits de santé (AGSENR 141009A-31) and the Comité de Protection des Personnes (ref: 2014-07-21). The study was financed by the European Leukodystrophy Association (ELA 2012-008l1), and medications provided by GlaxoSmithKline (MED 14006-HAO14008-NoVAL 2015/2014-115/02). All families gave written informed consent.   In this pilot study involving patients with Aicardi-Goutières syndrome  (AGS) due to mutations in TREX1, RNASEH2A, RNASEH2B or SAMHD1 three nucleoside analogue reverse transcriptase inhibitors (RTIs) were administered over 12 months. Patients were treated with triple therapy comprising abacavir (ABC), lamivudine (3TC) and zidovudine (AZT) according to a dosing protocol used in children infected with HIV-1 (https://aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf). HLA B57-01 status was determined before exposure to abacavir. Medication in syrup or tablet form was administered orally or by gastrostomy tube. Data on adverse events were collected in accordance with Article R1123-39 of the French Public Health Code and European Medicines Agency guidelines on good pharmacovigilance practice. Compliance was estimated from the count of bottles returned, mean corpuscular volume and a comparison of recorded drug concentrations with those observed in HIV-1 infected children (PMID: 25279808). Treatment was initiated on D0 and stopped at M12. All evaluations and sampling were undertaken at the Clinical Investigation Centre, Institut Imagine, Hôpital Necker, Paris, France, with visits at Day 0 (D0), and then at 1 (M1), 3 (M3), 6 (M6), 9 (M9), 12 (M12) and 18 (M18) months thereafter. RNA-seq was performed with samples taken at D0, M12 and M18. Total RNA extracted using a PreAnalytix RNA isolation kit. RNA integrity was analysed on an Agilent 2100 Bioanalyzer.  Truseq stranded mRNA Assay. Paired end.
attributes.tag: Experimental Factor: time
attributes.value: 18
attributes.tag: Experimental Factor: disease
attributes.value: Aicardi-Goutieres syndrome
attributes.tag: Experimental Factor: treatment
attributes.value: none