Hereditary neuropathy or pain disorder

Gene: OPA3

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 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

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Green List (high evidence)

Comment on mode of inheritance: Cases with peripheral neuropathy appear to be associated with autosomal dominant Optic atrophy 3 with cataract. This gene is also associated with a recessive condition in OMIM.

Created: 6 Nov 2024, 3:18 p.m. | Last Modified: 6 Nov 2024, 3:18 p.m.

Panel Version: 6.128

Associated with 3-methylglutaconic aciduria, type III, OMIM:258501 (AR) and Optic atrophy 3 with cataract, OMIM:165300 (AD).

PMID:28050599 - Bourne et al 2017 - 1 case - woman with cataracts, optic atrophy, lipodystrophy/lipoatrophy, and peripheral neuropathy. Exome sequencing identified a OPA3 c.235C > G p.(Leu79Val) variant that was confirmed to be de novo. The variant is not reported in gnomAD.

PMID: 31119193 - Horga et al 2019 - describe 2 families and one sporadic case with a syndromic form of OPA3-related autosomal dominant optic atrophy and cataract in which patients also show peripheral neuropathy. Heterozyous variants in OPA3 were identified c.23T>C (p.Met8Thr), c.313C>G (p.Gln105Glu) and c.313C>G (p.Gln105Glu) in each of the 3 families. In 4 patients, the peripheral neuropathy was a major cause of disability or was severe enough to motivate the referral to specialists.

PMID:21036400 - Yu-Wai-Man et al 2011 - no patients with OPA3 variants reported, only OPA1 variants.

Created: 6 Nov 2024, 3:16 p.m. | Last Modified: 6 Nov 2024, 3:17 p.m.

Panel Version: 6.127

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Optic atrophy 3 with cataract, OMIM:165300

Publications

• 28050599
• 31119193

I don't know

Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broader phenotype: 3-methylglutaconic aciduria type III

Created: 7 Dec 2019, 12:03 a.m. | Last Modified: 7 Dec 2019, 12:03 a.m.

Panel Version: 0.86

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, 10:25 p.m. | Last Modified: 6 Dec 2019, 10:25 p.m.

Panel Version: 0.84

Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.

Created: 11 Jun 2019, 1:40 p.m.

Green List (high evidence)

Peripehral neuropathy reported in multiple unrelated individuals and should be included in panel

Created: 20 Oct 2024, 10:21 a.m. | Last Modified: 20 Oct 2024, 10:21 a.m.

Panel Version: 5.19

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Infantile optic atrophy, additionally, extra pyramidal disorder (chorea), ataxia, cognitive defects, axonal sensory neuropathy, autonomic neuropathy, pseudo-obstruction

Publications

• 28050599: 21036400 : 31119193: