The SLC52A2 gene has been associated with autosomal recessive Brown-Vialetto-Van Laere syndrome using the ClinGen Clinical Validity Framework as of 9/12/2017. This association was made using case-level data only. At least 12 missense and nonsense variants have been reported in humans. SLC52A2 was first associated with this disease in humans as early as 2012 (Johnson et al.). SLC52A2 is associated with the childhood onset neurodegenerative syndrome Brown–Vialetto–Van Laere (BVVL) which is characterized by sensorineural hearing loss and ponto-bulbar palsy (PMID: 22864630, 30420458). Whilst these are the most common clinical features, BVVL can also present without either symptom (PMID: 26973221). The standard treatment for BVVL is riboflavin supplementation which is associated with favourable clinical outcomes (PMID: 26973221). 10 probands in 7 publications (22740598, 22864630, 23243084, 24616084, 24253200, 25807286, 29053833) are included in this curation. Variants in this gene segregated with disease in 5 additional family members. More evidence is available in the literature, but the maximum score for genetic evidence and/or experimental evidence (12 pts.) has been reached. This gene-disease association is supported by expression studies and in vitro assays. In summary, SLC52A2 is definitively associated with autosomal recessive Brown-Vialetto-Van Laere syndrome.
This gene-disease pair was originally evaluated by the ClinGen Hearing Loss GCEP on 7/9/2018. It was reevaluated on 6/21/2023 in collaboration with the Amyotrophic Lateral Sclerosis Spectrum Disorders GCEP. As a result of this reevaluation, the classification did not change. However additional genetic evidence has been included and scoring adjusted to the current Gene Clinical Validity SOP Version 9. The new genetic evidence included 8 variants (5 missense, 1 frameshift, 1 nonsense, 1 small deletion) and 6 probands in 6 publications (PMID: 31064337, 30343981, 29961509, 29053833, 34737166, 27148561).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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