Genetic epilepsy syndromesGene: PNPT1
Reviewed for the intellectual disability panel. Seizures may be observed in affected individuals (details below). Please consider inclusion with amber / green rating.
Biallelic PNPT1 pathogenic variants cause Combined oxidative phosphorylation deficiency 13 (MIM 614932). Despite phenotypic variability - common to disorders resulting from mitochondrial dysfunction - DD and ID of relevant severity to the current panel have been reported in several individuals published in the literature. Seizures may also be observed.
Rius et al (2019 - PMID: 31752325) provide an overview of 24 affected individuals (7 new and 17 from previous studies). Neurodevelopmental features are summarized in fig.1 and additional details are provided in the supplement. Based on this review, seizures were present in 7 individuals (of the 18 for whom this information was available).
PNPT1 encodes the mitochondrial polynucleotide phosphorylase, involved in the import of nuclear-encoded RNA to mitochondria. Loss of its activity has been shown to result in combined respiratory chain deficiency. However, as discussed by Rius et al and previous articles as well, OXPHOS studies in affected individuals may be normal or suggestive of only mild impairment due to tissue specificity and different assay methods used (eg. spectrophotometric vs dipstick activity assays). The same applies to lactate which was normal or mildly elevated in some affected individuals.
Missense, pLoF function variants as well as a synonymous one leading to aberrant splicing (NM_033109.4:c.1818T>G) have been reported.
Created: 28 Nov 2019, 6:18 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Combined oxidative phosphorylation deficiency 13, MIM 614932
gene: PNPT1 was added gene: PNPT1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: PNPT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNPT1 were set to 31752325 Phenotypes for gene: PNPT1 were set to Combined oxidative phosphorylation deficiency 13, MIM 614932 Penetrance for gene: PNPT1 were set to Complete Review for gene: PNPT1 was set to GREEN