Optic neuropathy

Gene: SLC52A2

Green List (high evidence)

SLC52A2 (solute carrier family 52 member 2)
EnsemblGeneIds (GRCh38): ENSG00000185803
EnsemblGeneIds (GRCh37): ENSG00000185803
OMIM: 607882, Gene2Phenotype
SLC52A2 is in 18 panels

3 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on classification of this gene: The rating for this gene should be added as GREEN, as this gene has been implicated in optic atrophy, as identified from biallelic loss-of-function variants from >20 unrelated individuals/ families from multiple ethnicities and supported by results from functional studies. Several of these patients with biallelic variants in SLC52A2 gene and treated with oral riboflavin responded well to the treatment.

Unrelated individuals carrying homozygous variants (e.g. c.916G>A/ p.Gly306Arg) and compound heterozygous variants (e.g. c.368T>C/ p.Leu123Pro & c.1016T>C/ p.Leu339Pro) were reported with Brown-Vialetto-Van Laere syndrome-2. According to report from Foley et al (2014), patients were presented with ataxia (9 out of 18 patients), hearing loss (all 18 patients), limb/ muscle weakness (17 patients), optic atrophy/ impaired vision (14 of 15 patients), tongue fasciculations (11 of 18 patients) and axonal sensorimotor neuropathy (all 18 patients). The onset of ataxia ranged from 1.5 to 8 years of age and some of these patients were confined to a wheelchair in their childhood (ranging from 1.5 to 8 years old). Respiratory insufficiency developed in 13 patients (PMID:24253200). One patient from this study and patient from Ciccolella et al (2012) bearing compound heterozygous variants were hospitalized for respiratory failure and died at 3-4 years of age (PMID:24253200; PMID:23243084).

A report on an eight year old patient with already identified homozygous variant (c.916G>A/ p.Gly306Arg) was presented with progressive ataxia since the age of 2.5 years and cerebellar atrophy and peripheral polyneuropathy despite the absence of other common symptoms of Brown-Vialetto-Van Laere syndrome including motor neuropathy, bulbar palsy, optic atrophy, and sensorineural hearing loss (PMID:30377535).

A recent review and statistical analysis by Zhou et al reports data of 62 BVVL type 2 patients from 43 different families, of which 40 patients had homozygous and 22 patients had compound heterozygous variants. A total of 32 variants have been reported to date, with the most common being missense variants. The symptoms of BVVL type 2 appear at the earliest shortly after birth and at the latest at 10 years of age. The most common symptoms are hearing loss (83.9%), muscle weakness (80.6%), visual impairment (64.5%), and ataxia (61.3%) (PMID:36186484).

Transfection and overexpression of SLC52A2 gene containing mutant alleles in HEK293 showed that the riboflavin uptake activity was abolished in certain mutants and moderately reduced in others. In addition, the expression levels of mutants were decreased (in correlation with the reduction in activity) with the exception of only one mutant tested (PMID:22864630; PMID:24253200).
Created: 11 Dec 2022, 7:26 p.m. | Last Modified: 11 Dec 2022, 7:26 p.m.
Panel Version: 3.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867; Optic atrophy, MONDO:0003608

Publications

Tom Cullup (Great Ormond Street Hospital)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Brown-Vialetto-Van Laere syndrome 2, 614707

Publications

Ellen McDonagh (Genomics England Curator)

Added this gene to this panel after discussion with the Genomics England Clinical Team. This gene is green on several of our other gene panels for Brown-Vialetto van later syndrome 2. In the OMIM clinical synopsis for this, absent pupillary reflex, Nystagmus and Visual loss is one of the clinical features on the clinical synopsis. The eligibility statement for optic neuropathies panel includes: “Optic atrophy occurring either in isolation or in association with other multisystemic features”, therefore syndromic forms are included. There is also a possible intervention available, and so it was felt it was suitable to include this gene as Green on this panel.
Created: 13 Aug 2018, 4:47 p.m.
Added the 'treatable' tag, as riboflavin treatment may be beneficial to patients.
Created: 13 Aug 2018, 4:45 p.m.

History Filter Activity

11 Dec 2022, Gel status: 3

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2, 614707 to Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867; Optic atrophy, MONDO:0003608

11 Dec 2022, Gel status: 3

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: SLC52A2 were set to 23243084; 22864630

19 Mar 2019, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source London North GLH was added to SLC52A2. Rating Changed from Green List (high evidence) to Green List (high evidence)

13 Aug 2018, Gel status: 3

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: slc52a2 has been classified as Green List (High Evidence).

13 Aug 2018, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SLC52A2 was added to Inherited optic neuropathies panel. Sources: Other

13 Aug 2018, Gel status: 1

Created

Ellen McDonagh (Genomics England Curator)

SLC52A2 was created by Ellen McDonagh