Possible mitochondrial disorder - nuclear genes

Gene: POLRMT

Green List (high evidence)

Comment on mode of inheritance: There are nine unrelated families with biallelic POLRMT variants and three unrelated families with monoallelic variants reported in the literature. Hence, this gene can be rated green with 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' as MOI.

Created: 12 Mar 2026, 2:33 p.m. | Last Modified: 12 Mar 2026, 2:42 p.m.

Panel Version: 4.23

Comment on phenotypes: OMIM phenotype was last accessed on 12 March 2026.

Created: 12 Mar 2026, 2:31 p.m. | Last Modified: 12 Mar 2026, 2:31 p.m.

Panel Version: 4.22

PMID:40583167 (2026) reported the identification of POLRMT variants in six new patients from six unrelated families. Five of these patients had biallelic variants and one patient had monoallelic POLRMT variant. The patients showed extended phenotypic abnormalities often presenting early in life with features including global developmental delay, cognitive impairment, short stature and muscular hypotonia.

Created: 12 Mar 2026, 2:30 p.m. | Last Modified: 12 Mar 2026, 2:30 p.m.

Panel Version: 4.20

The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 1:12 p.m. | Last Modified: 1 Feb 2023, 1:12 p.m.

Panel Version: 2.5

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 55, OMIM:619743; combined oxidative phosphorylation deficiency 55, MONDO:0859228

Publications

• 33602924
• 40583167

Green List (high evidence)

Gene list provided by Carl Fratter (Oxford University Hospitals NHS Trust) in August 2022 on behalf of the three GMS Mitochondrial providers, supporting the rating upgrade from Amber to Green on this panel.

Created: 30 Aug 2022, 9:26 a.m. | Last Modified: 30 Aug 2022, 9:26 a.m.

Panel Version: 1.102

Comment on list classification: There is now sufficient evidence to promote this gene to Green at the next GMS panel update.

POLRMT is associated with a relevant phenotype in OMIM (MIM# 619743). At least 8 individuals from 7 unrelated families reported in literature (PMID: 33602924) with distinct variant in this gene (5 biallelic, 2 monoallelic) associated with mitochondrial dysfunction and a broad spectrum of neurological presentations. Affected individuals presented with global developmental delay, hypotonia, short stature, and speech/intellectual disability in childhood; one subject displayed an indolent progressive external ophthalmoplegia phenotype.

Created: 29 Jul 2022, 2:42 p.m. | Last Modified: 29 Jul 2022, 2:42 p.m.

Panel Version: 1.90

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 55, OMIM: 619743

Publications

• 33602924

Comment on list classification: After feedback from the Genomics England Clinical Team, this gene should be kept Amber as there is currently no published cases.

Created: 5 Jun 2019, 1:22 p.m.

Comment on list classification: Promoted from Red to Amber.

Created: 10 May 2019, 2:20 p.m.

Green List (high evidence)

Updated information and Green review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: Poster from Newcastle team at UK Neuromuscular conference 2019 with several cases (both recessive and dominant cases)

Created: 10 May 2019, 1:02 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
No OMIM phenotype

Publications

• none found