Adult onset hereditary spastic paraplegia
Gene: C12orf65The 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
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
Added new-gene-name tag, new approved HGNC gene symbol for C12orf65 is MTRFRCreated: 24 Feb 2021, 2:48 p.m. | Last Modified: 24 Feb 2021, 2:48 p.m.
Panel Version: 1.16
Childhood onset.Created: 20 Sep 2020, 7:58 a.m. | Last Modified: 20 Sep 2020, 7:58 a.m.
Panel Version: 1.7
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.
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 panelCreated: 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
Tag Q3_21_expert_review was removed from gene: C12orf65. Tag Q3_21_phenotype was removed from gene: C12orf65.
Source Expert Review Amber was added to C12orf65. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Phenotypes for gene: C12orf65 were changed from Combined oxidative phosphorylation deficiency 7, OMIM:613559; Spastic paraplegia 55, autosomal recessive, OMIM:615035 to Spastic paraplegia 55, autosomal recessive, OMIM:615035
Phenotypes for gene: C12orf65 were changed from optic atrophy and spasticity, tibial muscle weakness and atrophy, peripheral neuropathy; Combined oxidative phosphorylation deficiency 7, 613559; Spastic paraplegia 55, autosomal recessive, 615035 to Combined oxidative phosphorylation deficiency 7, OMIM:613559; Spastic paraplegia 55, autosomal recessive, OMIM:615035
Publications for gene: C12orf65 were set to 23188110; 24424123
Tag Q3_21_expert_review tag was added to gene: C12orf65. Tag Q3_21_phenotype tag was added to gene: C12orf65.
Tag new-gene-name tag was added to gene: C12orf65.
Publications for gene: C12orf65 were set to
Source Yorkshire and North East GLH was added to C12orf65.
Source Expert Review Green was added to C12orf65. Mode of inheritance for gene C12orf65 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes optic atrophy and spasticity, tibial muscle weakness and atrophy, peripheral neuropathy; Combined oxidative phosphorylation deficiency 7, 613559; Spastic paraplegia 55, autosomal recessive, 615035 for gene: C12orf65 Rating Changed from Red List (low evidence) to Green List (high evidence)
Source NHS GMS was added to C12orf65.
gene: C12orf65 was added gene: C12orf65 was added to Hereditary spastic paraplegia - adult onset. Sources: London North GLH Mode of inheritance for gene: C12orf65 was set to