RT Journal Article
SR Electronic
T1 Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both?
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 204
OP 208
DO 10.1136/jmedgenet-2020-107367
VO 59
IS 2
A1 Pennisi, Alessandra
A1 Rötig, Agnès
A1 Roux, Charles-Joris
A1 Lévy, Raphaël
A1 Henneke, Marco
A1 Gärtner, Jutta
A1 Teke Kisa, Pelin
A1 Sarioglu, Fatma Ceren
A1 Yiş, Uluç
A1 Konczal, Laura L
A1 Burkardt, Deepika D
A1 Wu, Sulin
A1 Gaignard, Pauline
A1 Besmond, Claude
A1 Hubert, Laurence
A1 Rio, Marlène
A1 Barcia, Giulia
A1 Munnich, Arnold
A1 Boddaert, Nathalie
A1 Schiff, Manuel
YR 2022
UL http://jmg.bmj.com/content/59/2/204.abstract
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.