Expanding the Genetic and Phenotypic Spectrum of <scp> <i>POLRMT</i> </scp> ‐Related Mitochondrial Disease
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
- Larissa Mattern (ORCID: https://orcid.org/0000-0003-1233-5652)
- Claes M. Gustafsson (ORCID: https://orcid.org/0000-0003-3531-8468)
- Ingo Kurth (ORCID: https://orcid.org/0000-0002-5642-8378)
- Saskia Brigitte Wortmann (ORCID: https://orcid.org/0000-0002-1968-8103)
- Katrin Õunap (ORCID: https://orcid.org/0000-0002-4594-6364)
- T. Herberhold
- Miriam Elbracht (ORCID: https://orcid.org/0000-0001-5088-1369)
- Helen McCullagh (ORCID: https://orcid.org/0000-0003-4896-5111)
- Monika Oláhová (ORCID: https://orcid.org/0000-0002-4082-3875)
- Charlotte V. Y. Knowles
- Jack J. Collier (ORCID: https://orcid.org/0000-0001-6282-0301)
- Robert McFarland (ORCID: https://orcid.org/0000-0002-8833-2688)
- Eleni Mavraki
- Sebastian Valenzuela (ORCID: https://orcid.org/0000-0001-5153-8431)
- Carol Saunders (ORCID: https://orcid.org/0000-0002-7407-7735)
- André Reis (ORCID: https://orcid.org/0000-0002-6301-6363)
- Mahmoud R. Fassad (ORCID: https://orcid.org/0000-0003-2568-8326)
- Andrea Maier (ORCID: https://orcid.org/0000-0002-3427-4806)
- Lei Zhang (ORCID: https://orcid.org/0000-0001-7242-5292)
- Robert William Taylor (ORCID: https://orcid.org/0000-0002-7768-8873)
- Nergis Güzel (ORCID: https://orcid.org/0009-0002-1030-2179)
Institutions
- Montreal Neurological Institute and Hospital (CA)
- Children's Mercy Hospital (US)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Paracelsus Medical University (AT)
- Leeds Teaching Hospitals NHS Trust (GB)
- Sahlgrenska University Hospital (SE)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- Tartu University Hospital (EE)
- Northumbria University (GB)
- Schön Klinik Vogtareuth (DE)
- Wellcome Centre for Mitochondrial Research (GB)
- McGill University (CA)
- University of Missouri–Kansas City (US)
- Alexandria University (EG)
- University of Gothenburg (SE)
- RWTH Aachen University (DE)
Publication Details
- Journal
- Clinical Genetics
- Published
- 2025-06-29
- DOI
- https://doi.org/10.1111/cge.70011
- Citations
- 1
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Fight for Sight
- LifeArc
- Swedish Cancer Foundation
- National Institute for Health and Care Research
- Pathological Society of Great Britain and Ireland
- Eesti Teadusagentuur
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Lily Foundation
- Medical Research Council
- Wellcome Trust Centre for Mitochondrial Research