PT  - JOURNAL ARTICLE
AU  - Pennisi, Alessandra
AU  - Rötig, Agnès
AU  - Roux, Charles-Joris
AU  - Lévy, Raphaël
AU  - Henneke, Marco
AU  - Gärtner, Jutta
AU  - Teke Kisa, Pelin
AU  - Sarioglu, Fatma Ceren
AU  - Yiş, Uluç
AU  - Konczal, Laura L
AU  - Burkardt, Deepika D
AU  - Wu, Sulin
AU  - Gaignard, Pauline
AU  - Besmond, Claude
AU  - Hubert, Laurence
AU  - Rio, Marlène
AU  - Barcia, Giulia
AU  - Munnich, Arnold
AU  - Boddaert, Nathalie
AU  - Schiff, Manuel
TI  - Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both?
AID  - 10.1136/jmedgenet-2020-107367
DP  - 2022 Feb 01
TA  - Journal of Medical Genetics
PG  - 204--208
VI  - 59
IP  - 2
4099  - http://jmg.bmj.com/content/59/2/204.short
4100  - http://jmg.bmj.com/content/59/2/204.full
SO  - J Med Genet2022 Feb 01; 59
AB  - 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.