Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both?
| Autor: | Laurence Hubert, Marlène Rio, Nathalie Boddaert, Uluç Yiş, Sulin Wu, Laura L Konczal, Giulia Barcia, Claude Besmond, Fatma Ceren Sarioglu, Arnold Munnich, Manuel Schiff, Alessandra Pennisi, Pelin Teke Kisa, Charles-Joris Roux, Pauline Gaignard, Raphael Levy, Jutta Gärtner, Deepika D Burkardt, Marco Henneke, Agnès Rötig |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Pathology medicine.medical_specialty Mitochondrial Diseases Mitochondrial disease Neuroimaging Disease Mitochondrion Leukoencephalopathy Mitochondrial Proteins 03 medical and health sciences 0302 clinical medicine Immune system Interferon Leukoencephalopathies Genetics medicine Humans Child Genetics (clinical) 030304 developmental biology 0303 health sciences Whole Genome Sequencing business.industry RNA Brain medicine.disease Pathophysiology Child Preschool Exoribonucleases Interferon Type I Leigh Disease business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of medical genetics. 59(2) |
| ISSN: | 1468-6244 |
| Popis: | BackgroundBiallelic 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 methodsTo document neuroimaging data in six patients with PNPT1 highlighting novel findings.ResultsTwo 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.ConclusionWe 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. |
| Databáze: | OpenAIRE |
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