Mitochondrial disorders

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, 2:38 p.m. | Last Modified: 12 Mar 2026, 2:42 p.m.

Panel Version: 9.45

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

Created: 12 Mar 2026, 2:34 p.m. | Last Modified: 12 Mar 2026, 2:34 p.m.

Panel Version: 9.44

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, 2:34 p.m. | Last Modified: 12 Mar 2026, 2:34 p.m.

Panel Version: 9.43

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

Created: 1 Feb 2023, 12:16 p.m. | Last Modified: 1 Feb 2023, 12:16 p.m.

Panel Version: 3.6

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

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 7 unrelated families reported in literature (PMID: 33602924) with distinct variant in this gene associated with mitochondrial dysfunction and a broad spectrum of neurological presentations.

Created: 29 Jul 2022, 2:41 p.m. | Last Modified: 29 Jul 2022, 2:41 p.m.

Panel Version: 2.112

Green List (high evidence)

8 individuals from 7 families reported. 5 families with bi-allelic variants and 2 with heterozygous variants. 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: 5 Mar 2021, 6:39 a.m. | Last Modified: 5 Mar 2021, 6:39 a.m.

Panel Version: 2.20

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Mitochondrial disorder; intellectual disability; hypotonia

Publications

• 33602924

Variants in this GENE are reported as part of current diagnostic practice

I don't know

Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group.

Created: 23 Jul 2019, 10:13 a.m. | Last Modified: 23 Jul 2019, 10:13 a.m.

Panel Version: 1.412