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Lookup NU author(s): Professor Wyatt YueORCiD, Professor Robert TaylorORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2026.Biallelic hypomorphic variants in PRORP cause the rare autosomal recessive disorder combined oxidative phosphorylation deficiency type 54 (COXPD54). COXPD54 encompasses a clinical spectrum of sensorineural hearing loss and ovarian insufficiency (Perrault syndrome) to leukodystrophy with developmental delay and epilepsy. Here, we report two new affected individuals with biallelic PRORP variants with clinical features consistent with COXPD54. One individual was homozygous for c.1505G > A p.Arg502Gln, whereas the other was compound heterozygous for c.1510C > T, p.His504Tyr and c.893C > A, p.Ser298Ter (NM_014672.4). In vitro tRNA processing assays revealed decreased mitochondrial 5′ tRNA leader cleavage by human RNase P complex with the two novel missense PRORP metallonuclease domain variants. These data provide further evidence that biallelic PRORP variants disrupt 5’ tRNA leader cleavage and are associated with a pleiotropic phenotype of COXPD54.
Author(s): Lai KL, Smith TB, Maroofian R, Zaki MS, Ramadesikan S, Reynolds T, Koboldt DC, Hunter JM, Vidaurre J, Atanasova M, Marsden BD, Yue WW, Houlden H, Taylor RW, Newman WG, O'Keefe RT
Publication type: Article
Publication status: Published
Journal: Neurogenetics
Year: 2026
Volume: 27
Issue: 1
Print publication date: 03/03/2026
Online publication date: 03/03/2026
Acceptance date: 19/02/2026
Date deposited: 16/03/2026
ISSN (print): 1364-6745
ISSN (electronic): 1364-6753
Publisher: Springer
URL: https://doi.org/10.1007/s10048-026-00892-5
DOI: 10.1007/s10048-026-00892-5
Data Access Statement: The PRORP variants were submitted to ClinVar (https:/ /www.nc bi.nlm. nih.g ov/clinvar/) (GenBank: NM_014672.4; accession numbers SCV1705405, SCV007114217 and SCV007114218.
PubMed id: 41772230
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