Journal article

Clinical Spectrum and Functional Consequences Associated with Bi-Allelic Pathogenic PNPT1 Variants

Rocio Rius, Nicole J Van Bergen, Alison G Compton, Lisa G Riley, Maina P Kava, Shanti Balasubramaniam, David J Amor, Miriam Fanjul-Fernandez, Mark J Cowley, Michael C Fahey, Mary K Koenig, Gregory M Enns, Simon Sadedin, Meredith J Wilson, Tiong Y Tan, David R Thorburn, John Christodoulou

Journal of Clinical Medicine | MDPI AG | Published : 2019

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 patients with bi-allelic PNPT1 variants, we captured detailed clinical and molecular phenotypes of all 17 patients reported in the literature, plus seven new patients, including a 78-year-..

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Grants

Awarded by Australian Genomics Health Alliance (Australian Genomics) project - NHMRC Targeted Call for Research grant


Awarded by NHMRC


Awarded by National Heart, Lung and Blood Institute


Awarded by National Human Genome Research Institute


Funding Acknowledgements

This research was supported by: A New South Wales Office of Health and Medical Research (OHMR) Council Sydney Genomics Collaborative grant (JC); the Australian Genomics Health Alliance (Australian Genomics) project, funded by an NHMRC Targeted Call for Research grant (GNT1113531; JC, DRT); NHMRC research fellowship 1155244 (DRT); OHMR Fellowship (MJC); and a CONACYT Postgraduate Research Scholarship (RR). Sequencing and analysis were provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and were funded by the National Human Genome Research Institute, the National Eye Institute, the National Heart, Lung and Blood Institute grant UM1 HG008900, and, in part, by a National Human Genome Research Institute grant R01 HG009141.