Mitochondrial DNA maintenance disorder

Gene: SSBP1

Green List (high evidence)

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

Created: 1 Feb 2023, 12:55 p.m. | Last Modified: 1 Feb 2023, 12:55 p.m.

Panel Version: 2.3

Green List (high evidence)

Gene list provided by Carl Fratter (Oxford University Hospitals NHS Trust) in August 2022 on behalf of the three GMS Mitochondrial providers, indicating that this gene requires a rating upgrade from Amber to Green. MOI has also been updated from unknown to both mono- and biallelic inline with this review. Carl Fratter mentions additional cases have been seen within NHS GMS (not published).

Created: 30 Aug 2022, 9:10 a.m. | Last Modified: 30 Aug 2022, 9:10 a.m.

Panel Version: 1.14

At least 9 dominant families/cases and 2 recessive with optic atrophy with/without additional clinical features, including retinal macular dystrophy, sensorineural deafness, mitochondrial myopathy, and kidney failure. Supporting evidence in functional assays and zebrafish model.

Created: 30 Aug 2022, 9:08 a.m. | Last Modified: 30 Aug 2022, 9:08 a.m.

Panel Version: 1.13

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Optic atrophy 13 with retinal and foveal abnormalities, OMIM:165510

Publications

• 34905022
• 31550240
• 31550237
• 31298765
• 31479473

Green List (high evidence)

The publications above indicate that pathogenic variants cause disease via a dominant negative effect.
7 different variants have been reported in 9 unrelated families/individuals.
Only one variant has been reported in association with biallelic (autosomal recessive) inheritance to date; i.e. the majority of reported cases are of monoallelic (autosomal dominant) inheritance.
Green rating has been proposed by the GMS Mitochondrial specialist test group on the basis of the evidence summarised here.

Created: 12 Nov 2019, 5:25 p.m. | Last Modified: 12 Nov 2019, 5:25 p.m.

Panel Version: 1.0

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
optic atrophy; optic atrophy with additional features (including retinal degeneration)

Publications

• PMID: 31298765
• 31550240

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Comment on list classification: Confirmed on the NHSE GMS Mitochondrial Specialist Group Meeting call on 25th February 2019 that this gene should be Red on this panel as there is currently insufficient evidence in the literature.

Created: 25 Feb 2019, 4:35 p.m.

Red List (low evidence)

Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group. Gene Symbol submitted: SSBP1; Suggested intial gene rating: Red. Information provided: Mode of inheritance and phenotype

Created: 1 Feb 2019, 4:28 p.m.

Mode of inheritance
Unknown

Phenotypes
No OMIM phenotype