Optic neuropathy
Gene: SSBP1The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 1:02 p.m. | Last Modified: 30 Jan 2023, 1:02 p.m.
Panel Version: 3.7
The moi for this gene should be changed to BOTH monoallelic and Biallelic as PMID: 34905022 & 3155024 report two cases of SSBP1-disease associated with biallelic SSBP1 variants. The variant c.380G>A p.(Arg127Gln)(MAF of 0.00004) was found with c.394A>G p.(Ile132Val)(PMID: 34905022), which had previously been found as a homozygote in a single case (PMID: 31550240).Created: 4 Jan 2022, 4:06 p.m. | Last Modified: 4 Jan 2022, 5:13 p.m.
Panel Version: 2.56
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Multiple reports indicate that missense variants in SSBP1 cause optic atrophy with variable degree of retinal degeneration. Some families in addition to ophthalmic phenotype showed systemic involvement. Recurrent variants were identified by independent study groups.
Findings were supported by functional work in animal models.Created: 4 Feb 2021, 10:28 a.m. | Last Modified: 4 Feb 2021, 10:28 a.m.
Panel Version: 2.29
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Optic atrophy with retinal degeneration (+-systemic features)
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Three heterozygous missense variants in two families and two singletons. A postulated dominant-negative mechanism is supported by functional studies in zebrafish.Created: 16 Jul 2019, 3:04 p.m. | Last Modified: 16 Jul 2019, 3:04 p.m.
Panel Version: 1.114
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Autosomal dominant optic atrophy
Publications
Mode of pathogenicity
Other
Sources: Expert list
Variants identified to date are missense and putative mode of action is dominant-negative, therefore there is potential for exception to loss-of-function rule, but insufficient data to clearly demonstrate at the moment. There are lower than expected LoF variants in gnomAD, so cannot rule out pathogenic LoF variants.Created: 16 Jul 2019, 2:22 p.m. | Last Modified: 16 Jul 2019, 2:31 p.m.
Panel Version: 1.114
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Autosomal dominant optic atrophy with variable retinal degeneration
Publications
Gene: ssbp1 has been classified as Green List (High Evidence).
Tag Q1_22_MOI was removed from gene: SSBP1.
Source NHS GMS was added to SSBP1. Mode of inheritance for gene SSBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Rating Changed from Green List (high evidence) to Red List (low evidence)
Tag Q1_22_MOI tag was added to gene: SSBP1.
Phenotypes for gene: SSBP1 were changed from Optic atrophy 13 with retinal and foveal abnormalities, OMIM:165510; Autosomal dominant optic atrophy with variable retinal degeneration; Optic atrophy with retinal degeneration (+-systemic features) to Optic atrophy 13 with retinal and foveal abnormalities OMIM:165510
Publications for gene: SSBP1 were set to 31298765; 31550240; 31550237; 30412255
Phenotypes for gene: SSBP1 were changed from Autosomal dominant optic atrophy with variable retinal degeneration to Optic atrophy 13 with retinal and foveal abnormalities, OMIM:165510; Autosomal dominant optic atrophy with variable retinal degeneration; Optic atrophy with retinal degeneration (+-systemic features)
Publications for gene: SSBP1 were set to 31298765
Publications for gene: SSBP1 were set to PMID: 31298765
Gene: ssbp1 has been classified as Green List (High Evidence).
gene: SSBP1 was added gene: SSBP1 was added to Optic neuropathy. Sources: Expert list Mode of inheritance for gene: SSBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SSBP1 were set to PMID: 31298765 Phenotypes for gene: SSBP1 were set to Autosomal dominant optic atrophy with variable retinal degeneration Penetrance for gene: SSBP1 were set to Complete Review for gene: SSBP1 was set to GREEN