Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both?. Issue 2 (16th November 2020)

• Record Type: Journal Article
• Authors: Pennisi, Alessandra; Rötig, Agnès; Roux, Charles-Joris; Lévy, Raphaël; Henneke, Marco; Gärtner, Jutta; Teke Kisa, Pelin; Sarioglu, Fatma Ceren; Yiş, Uluç; Konczal, Laura L; Burkardt, Deepika D; Wu, Sulin; Gaignard, Pauline; Besmond, Claude; Hubert, Laurence; Rio, Marlène; Barcia, Giulia; Munnich, Arnold; Boddaert, Nathalie; Schiff, Manuel
• Is Part Of: Journal of medical genetics. Volume 59:Issue 2(2022)
• Page Start: 204
• Page End: 208
• Publication Date: 2020-11-16
• Subjects: brain diseases -- metabolic; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2020-107367
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: Biallelic variants in PNPT1 cause a mitochondrial disease of variable severity. PNPT1 (polynucleotide phosphorylase) is a mitochondrial protein involved in RNA processing where it has a dual role in the import of small RNAs into mitochondria and in preventing the formation and release of mitochondrial double-stranded RNA into the cytoplasm. This, in turn, prevents the activation of type I interferon response. Detailed neuroimaging findings in PNPT1-related disease are lacking with only a few patients reported with basal ganglia lesions (Leigh syndrome) or non-specific signs. Objective and methods: To document neuroimaging data in six patients with PNPT1 highlighting novel findings. Results: Two patients exhibited striatal lesions compatible with Leigh syndrome; one patient exhibited leukoencephalopathy and one patient had a normal brain MRI. Interestingly, two unrelated patients exhibited cystic leukoencephalopathy resembling RNASET2-deficient patients, patients with Aicardi-Goutières syndrome (AGS) or congenital CMV infection. Conclusion: We suggest that similar to RNASET2, PNPT1 be searched for in the setting of cystic leukoencephalopathy. These findings are in line with activation of type I interferon response observed in AGS, PNPT1 and RNASET2 deficiencies, suggesting a common pathophysiological pathway and linking mitochondrial diseases, interferonopathies and immune dysregulations.