Mitochondrial disorders

Gene: PITRM1

Green List (high evidence)

Three families with two unique variants. Mitochondrial dysfunction identified in in vitro functional assays and mouse model.

Created: 23 Mar 2020, 12:23 a.m. | Last Modified: 23 Mar 2020, 12:23 a.m.

Panel Version: 2.5

Phenotypes
Cerebellar atrophy; mental retardation; spinocerebellar ataxia; cognitive decline; psychosis

Publications

• 26697887
• 29764912

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

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 10:34 a.m. | Last Modified: 2 May 2024, 10:34 a.m.

Panel Version: 6.3

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 24 Aug 2023, 3:54 p.m. | Last Modified: 24 Aug 2023, 3:54 p.m.

Panel Version: 4.86

The review article "Role of PITRM1 in Mitochondrial Dysfunction and Neurodegeneration" (PMID:34356897) outlines the role of PITRM1 in normal mitochondrial function, it also presents the published evidence which demonstrates the consequences of variant PITRM1, in humans and functional studies.

Created: 24 Aug 2023, 3:41 p.m. | Last Modified: 24 Aug 2023, 3:41 p.m.

Panel Version: 4.85

Green rating based on publications pmids 29764912; 26697887; 29383861

Created: 20 Aug 2019, 12:37 p.m. | Last Modified: 17 Sep 2019, 10:24 a.m.

Panel Version: 1.485

Comment on list classification: This gene is being demoted to amber as it has not been reviewed as green by the GMS Mitochondrial specialist test group.

Created: 20 Aug 2019, 12:19 p.m. | Last Modified: 20 Aug 2019, 12:19 p.m.

Panel Version: 1.478

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 33835239
• 34356897

Comment on list classification: PITRM1 identified by expert review by Konstantinos Varvagiannis on Intellectual Disability Panel https://panelapp.genomicsengland.co.uk/panels/285/.

Currently no OMIM or G2P phenotypes terms associated with the gene.

PMID: 29764912 reports on 2 consanguineous Palestinian families each with 2 affected boys. Both Palenstinian families are from Arab descent but are from different locale. PMID: 26697887 reports 2 siblings from a consanguineous Norwegian family homozygous for a missense variant (NM_014889.2:c.548G> or p.Arg183Gln). Although there is some functional work (PMID: 29383861) phenotypes are varied in severity.

There are sufficient unrelated families (>3) for PITRM1 to be classified as Green and PITRM1 is a mitochondrial matrix enzyme so therefore relevant to this panel.

Created: 18 Jul 2019, 4:19 p.m. | Last Modified: 18 Jul 2019, 4:19 p.m.

Panel Version: 1.410

Comment on list classification: This should be added to the red list until further evidence arised. PMID: 26697887 reports two siblings homozygous for a PITRM1 variant (c.548G>A, p.Arg183Gln), which was followed up by functional studies in vitro. A PITRM1 +/- mouse model showed progressive ataxia and accumulation of amyloid deposits. Is not a gene within G2P or OMIM databases associated with a disorder.

Created: 2 Mar 2016, 1:48 p.m.

Green List (high evidence)

single mutation report in literature

Created: 7 Feb 2016, 8:40 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal