Adult onset hereditary spastic paraplegia

Gene: C12orf65

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

Created: 14 Mar 2022, 1:19 p.m. | Last Modified: 14 Mar 2022, 1:19 p.m.

Panel Version: 1.95

I don't know

Review of literature showed that C12orf65 is associated with a childhood-onset condition (MIM# 300534). However, the presenting features are optic atrophy and variable ID arising within the first decade of life, while progressive spastic paraparesis may only becomes evident by the second decade (PMID: 24424123; 26380172) - although earlier onset has also been reported (PMID: 24284555; 25995486). Several publications describe adult patients presenting with spasticity but the age of onset is not clear from some case reports (PMID: 23188110; 24198383; 24080142).

Leaving the rating as Green, but with a recommendation for review at the next GMS panel update to assess whether this gene is appropriate for this adult onset panel (tagged Q3_21_phenotype). Inclusion may be justified to ensure identification of edge cases.

This gene is already Green on the 'Hereditary spastic paraplegia - childhood onset v.2.18' panel.

Created: 23 Aug 2021, 3:03 p.m. | Last Modified: 23 Aug 2021, 3:03 p.m.

Panel Version: 1.52

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 55, autosomal recessive, OMIM:615035

Publications

• 23188110
• 24080142
• 24198383
• 24284555
• 24424123
• 25995486
• 26380172

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

Created: 24 Feb 2021, 2:48 p.m. | Last Modified: 24 Feb 2021, 2:48 p.m.

Panel Version: 1.16

Red List (low evidence)

Childhood onset.

Created: 20 Sep 2020, 7:58 a.m. | Last Modified: 20 Sep 2020, 7:58 a.m.

Panel Version: 1.7

I don't know

Childhood onset only.

Created: 8 May 2019, 4:23 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 23188110
• 24424123

I don't know

Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.

Created: 21 May 2019, 4:14 p.m.

Review and rating submitted byJames Polke (Neurogenetics Laboratory,Institute of Neurology, London), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.

Created: 9 May 2019, 4:50 p.m.

Green List (high evidence)

Victoria: Nerve conduction studies showed decreased motor and sensory nerve conduction velocities, and sural nerve biopsy showed decreased number of large-diameter nerve fibers, onion bulb-like structures, and endoneural fibrosis. Mutations published in 3 families, Japanese brothers, 2 sibs in consanguineous family, and 3 individual from indan consanguineous family. In Sheffields HSP panel

Created: 25 Apr 2019, 1:22 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 55, autosomal recessive, 615035; optic atrophy and spasticity, tibial muscle weakness and atrophy, peripheral neuropathy; Combined oxidative phosphorylation deficiency 7, 613559