Document Type
Article
Publication Date
1-2026
Identifier
DOI: 10.1111/cge.70011; PMCID: PMC12674971
Abstract
Mitochondrial diseases are a complex group of conditions exhibiting significant phenotypic and genetic heterogeneity. Genomic testing is increasingly used as the first step in the diagnostic pathway for mitochondrial diseases. We used next-generation sequencing followed by bioinformatic data analysis to identify potentially damaging variants in the POLRMT gene (NM_005035.4) in six new affected individuals. Structural protein analysis predicted the detrimental impact of variants on POLRMT protein structure. Patients show extended phenotypic abnormalities often presenting early in life with features including global developmental delay, cognitive impairment, short stature and muscular hypotonia. This study expands the genetic and phenotypic landscape of mitochondrial disease associated with POLRMT variants.
Journal Title
Clinical genetics
Volume
109
Issue
1
First Page
167
Last Page
175
MeSH Keywords
Humans; Mitochondrial Diseases; Male; Phenotype; Female; Child; Child, Preschool; Mutation; Genetic Association Studies; High-Throughput Nucleotide Sequencing; Genetic Predisposition to Disease; Infant; Adolescent
PubMed ID
40583167
Keywords
POLRMT; mitochondrial disease; neurodevelopmental disorders; variant classification
Recommended Citation
Fassad MR, Valenzuela S, Oláhová M, et al. Expanding the Genetic and Phenotypic Spectrum of POLRMT-Related Mitochondrial Disease. Clin Genet. 2026;109(1):167-175. doi:10.1111/cge.70011
Comments
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Publisher's Link: https://onlinelibrary.wiley.com/doi/10.1111/cge.70011