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

Fassad MR, Valenzuela S, Oláhová M, Collier JJ, Knowles CV, Mavraki E, Elbracht M, Güzel N, Herberhold T, Kurth I, Maier A, Mattern L, Saunders C, McCullagh H, Õunap K, Wortmann SB, Reis A, Zhang L, Gustafsson CM, McFarland R, Taylor RW (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Clinical Genetics Wiley-Blackwell

DOI: 10.1111/cge.70011

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.

Authors with CRIS profile

André Wiesmann da Silva Reis Lehrstuhl für Humangenetik

Involved external institutions

Wellcome Centre for Mitochondrial Research GB United Kingdom (GB) University of Gothenburg / Göteborgs universitet SE Sweden (SE) Newcastle upon Tyne Hospitals NHS Foundation Trust GB United Kingdom (GB) Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen DE Germany (DE) Schön Klinik Vogtareuth DE Germany (DE) Universitätsklinikum Aachen (UKA) DE Germany (DE) Children's Mercy Hospital US United States (USA) (US) Leeds Teaching Hospitals NHS Trust GB United Kingdom (GB) Tartu University Hospital EE Estonia (EE) Universitätskliniken Salzburg AT Austria (AT)

How to cite

APA:

Fassad, M.R., Valenzuela, S., Oláhová, M., Collier, J.J., Knowles, C.V., Mavraki, E.,... Taylor, R.W. (2025). Expanding the Genetic and Phenotypic Spectrum of POLRMT-Related Mitochondrial Disease. Clinical Genetics. https://doi.org/10.1111/cge.70011

MLA:

Fassad, Mahmoud R., et al. "Expanding the Genetic and Phenotypic Spectrum of POLRMT-Related Mitochondrial Disease." Clinical Genetics (2025).

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