Hearing lossGene: SLC52A2
Comment on list classification: Changing rating from red to green. More than 3 cases reported in patients with Brown-Vialetto-Van Laere syndrome 2 and variants in this gene. Expert reviewer reports that hearing loss may be the first presentation.
Created: 11 May 2020, 12:02 p.m. | Last Modified: 11 May 2020, 12:02 p.m.
Panel Version: 2.18
Associated with Brown-Vialetto-Van Laere syndrome 2 #614707 (AR) in OMIM. Early childhood onset of sensorineural deafness is a feature along with bulbar dysfunction, and severe diffuse muscle weakness and wasting of the upper and lower limbs and axial muscles, resulting in respiratory insufficiency.
Numerous cases have been reported with variants in the SLC52A2 gene and Brown-Vialetto-Van Laere syndrome 2:
PMID: 22740598 Johnson et al 2012 - used linkage and exome sequencing to identify a novel mutation (p.G306R (c.916G>A)) in SLC52A2 in an extended Lebanese Brown-Vialetto-Van Laere kindred. The same homozygous mutation was identified in one additional subject from the UK, from 44 screened.
PMID: 22864630 Haack et al 2012 - exome sequencing of a single case with Brown-Vialetto-Van Laere syndrome showed compound heterozygosity for two pathogenic mutations in the SLC52A2 gene. Overexpression studies confirmed that the gene products of both mutant alleles have reduced riboflavin transport activities.
PMID: 23243084 Ciccolella et al 2013 - 1 case of a severe BVVL patient with two novel compound heterozygous mutations in SLC52A2 (c.155C>T, p.S52F and c.1255G>A, p.G419S). Functional studies show that these variants impair the gene expression of the corresponding transporter, resulting in a significant reduction of riboflavin transport.
PMID: 24253200 Foley et al 2014 - using exome and sanger sequencing identified 18 patients from 13 families with compound heterozygous or homozygous mutations in SLC52A2. Affected individuals share a core phenotype of rapidly progressive axonal sensorimotor neuropathy, hearing loss, optic atrophy and respiratory insufficiency. We demonstrate that SLC52A2 mutations cause reduced riboflavin uptake and reduced riboflavin transporter protein expression.
Created: 11 May 2020, 11:59 a.m. | Last Modified: 11 May 2020, 11:59 a.m.
Panel Version: 2.14
Gene suggested for panel by Dr Julia Rankin (Royal Devon and Exeter NHS Foundation Trust). Sensorineural deafness is the presenting feature in cases presenting after infancy with other neurology a year or 2 later – treatment with Riboflavin can be effective.
Sources: Expert list
Created: 11 May 2020, 9:59 a.m. | Last Modified: 11 May 2020, 10:01 a.m.
Panel Version: 2.9
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Brown-Vialetto-Van Laere syndrome 2 #614707
Tag for-review tag was added to gene: SLC52A2.
Tag treatable tag was added to gene: SLC52A2.
Gene: slc52a2 has been classified as Green List (High Evidence).
Phenotypes for gene: SLC52A2 were changed from to Brown-Vialetto-Van Laere syndrome 2 #614707
Publications for gene: SLC52A2 were set to
Mode of inheritance for gene: SLC52A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
gene: SLC52A2 was added gene: SLC52A2 was added to Hearing loss. Sources: Expert list Mode of inheritance for gene: SLC52A2 was set to Unknown