Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both?
J Med Genet
; 59(2): 204-208, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-33199448
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 ANDMETHODS:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Doença de Leigh
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Doenças Mitocondriais
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Proteínas Mitocondriais
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Exorribonucleases
Limite:
Adult
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Child
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Child, preschool
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article