Hereditary neuropathy or pain disorder

Gene: C12orf65

Green List (high evidence)

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

Created: 24 Feb 2025, 5:02 p.m. | Last Modified: 24 Feb 2025, 5:02 p.m.

Panel Version: 6.148

C12orf65 variants have been associated with Combined oxidative phosphorylation deficiency 7 (OMIM:613559); Spastic paraplegia 55, autosomal recessive (OMIM:615035). At least three variants have been reported in at least three unrelated cases, where peripheral neuropathy was evident (PMID: 24080142;23188110; 24424123; 24198383).

Created: 4 Nov 2024, 11:26 a.m. | Last Modified: 4 Nov 2024, 11:26 a.m.

Panel Version: 6.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 24198383
• 23188110
• 24424123
• 24080142

Added new-gene-name tag, new approved HGNC gene symbol for C12orf65 is MTRFR

Created: 24 Feb 2021, 2:53 p.m. | Last Modified: 24 Feb 2021, 2:53 p.m.

Panel Version: 1.23

Green List (high evidence)

Optic atrophy appears to be main feature with peripheral neuropathy as additional. PMID: 28091420- compound heterozygous for frameshift and nonsense variant in child who developed peripheral neuropathy developed after optic symptoms. PMID: 24198383- homozygous nonsense variant in 3 affected family members with axonal neuropathy and optic atrophy (2 brothers plus a cousin)

Created: 29 Apr 2019, 12:30 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 28091420
• 24198383

I don't know

Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.

Created: 6 Dec 2019, 2:09 p.m. | Last Modified: 6 Dec 2019, 2:09 p.m.

Panel Version: 0.33

Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.

Created: 9 May 2019, 5 p.m.

Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.

Created: 29 Apr 2019, 12:53 p.m.

Green List (high evidence)

Comment on mode of inheritance: Source: OMIM and G2P.

Created: 4 May 2016, 9:44 a.m.

Comment on list classification: Promoted from red to green due to expert review, and is a confirmed DD gene for combined oxidative phosphorylatuon deficiency 7. Associated with Combined oxidative phosphorylation deficiency 7 and Spastic paraplegia 55, autosomal recessive in OMIM.

Created: 4 May 2016, 9:44 a.m.

Green List (high evidence)

neuropathy is common

Created: 9 Dec 2015, 4:49 p.m.

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

Green List (high evidence)

PN in multiple affected individuals from different families

Created: 20 Oct 2024, 9:13 a.m. | Last Modified: 20 Oct 2024, 9:13 a.m.

Panel Version: 5.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
optic atrophy; spasticity; peripheral neuropathy

Publications

• 24080142: 23188110: 6303658: 24424123: 24198383

Complex HSP

Created: 8 Dec 2015, 3:06 p.m.