Expanding the Genetic and Phenotypic Spectrum of POLRMT-Related Mitochondrial Disease.

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All Authors

Fassad, MR.
Valenzuela, S.
Olahova, M.
Collier, JJ.
Knowles, CVY.
Mavraki, E.
Elbracht, M.
Guzel, N.
Herberhold, T.
Kurth, I.

LTHT Author

McCullagh, Helen

LTHT Department

Leeds Children's Hospital
Children's Neurosciences

Non Medic

Publication Date

2026

Item Type

Journal Article

Language

Subject

Subject Headings

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

Clinical Genetics