2019
DOI: 10.3390/jcm8112020
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Clinical Spectrum and Functional Consequences Associated with Bi-Allelic Pathogenic PNPT1 Variants

Abstract: PNPT1 (PNPase—polynucleotide phosphorylase) is involved in multiple RNA processing functions in the mitochondria. Bi-allelic pathogenic PNPT1 variants cause heterogeneous clinical phenotypes affecting multiple organs without any established genotype–phenotype correlations. Defects in PNPase can cause variable combined respiratory chain complex defects. Recently, it has been suggested that PNPase can lead to activation of an innate immune response. To better understand the clinical and molecular spectrum of pat… Show more

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Cited by 22 publications
(34 citation statements)
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“…Conversely, in Danio rerio (i.e., zebrafish) the expression pattern of the orthologous protein changes during development, being ubiquitous immediately after fertilization and becoming more and more restricted and limited to the tectum, the gill arches, and the developing ear at 48 h and 120 h post-fertilization [29]. Interestingly, in human, hearing loss is frequently associated with PNPT1 mutations, with or without other neurological symptoms depending on the mutations, and PNPT1 knock-out in inner ear hair cells causes hearing loss in mice [10,15,29]. PNPases are members of the PDX family of exoribonucleases [30] and in all organisms share a similar domain structure, consisting of two RNase PH like domains (RPH1 and RPH2), separated by an all-α-helical domain (AAHD), and followed by the KH and S1 RNA binding domains [31].…”
Section: Pnpt1 Regulation and Expression In Human Tissuesmentioning
confidence: 99%
See 2 more Smart Citations
“…Conversely, in Danio rerio (i.e., zebrafish) the expression pattern of the orthologous protein changes during development, being ubiquitous immediately after fertilization and becoming more and more restricted and limited to the tectum, the gill arches, and the developing ear at 48 h and 120 h post-fertilization [29]. Interestingly, in human, hearing loss is frequently associated with PNPT1 mutations, with or without other neurological symptoms depending on the mutations, and PNPT1 knock-out in inner ear hair cells causes hearing loss in mice [10,15,29]. PNPases are members of the PDX family of exoribonucleases [30] and in all organisms share a similar domain structure, consisting of two RNase PH like domains (RPH1 and RPH2), separated by an all-α-helical domain (AAHD), and followed by the KH and S1 RNA binding domains [31].…”
Section: Pnpt1 Regulation and Expression In Human Tissuesmentioning
confidence: 99%
“…zebrafish) the expression pattern of the orthologous protein changes during development, being ubiquitous immediately after fertilization and becoming more and more restricted and limited to the tectum, the gill arches, and the developing ear at 48h and 120h post-fertilization [29]. Interestingly, in human, hearing loss is frequently associated with PNPT1 mutations, with or without other neurological symptoms depending on the mutations, and PNPT1 knock-out in inner ear hair cells causes hearing loss in mice [10,15,29].…”
Section: Pnpt1 Regulation and Expression In Human Tissuesmentioning
confidence: 99%
See 1 more Smart Citation
“…These findings are underpinned by the knockout of PNPase or Suv3 that leads to an accumulation of dsRNA in the cytoplasm and an altered immune response [ 29 ]. Moreover, patients with bi-allelic PNPase variants showed increased levels of unprocessed mitochondrial transcripts and an enhanced expression of interferon-stimulated genes [ 30 ].…”
Section: Sources Of Endogenous Dsrnamentioning
confidence: 99%
“…The protective role of PNPase is of great importance, as revealed by the fact that mutations in PNPT1 (PNPase encoding gene) cause pathogenesis associated with the up-regulation of mt-dsRNA and interferon response [144,148]. A comparison of the type I interferon response across species, which involved 10 mammals and one bird, revealed PNPase as one of 62 core vertebrate interferon-stimulated genes [149].…”
Section: Mitochondrial Double-stranded Rna (Mt-dsrna) and The Innate mentioning
confidence: 99%