SLC22A25 was first reported in relation to autosomal recessive epileptic encephalopathy in 2005 (Molinari F, et al., 2005, PMID: 15592994) . At least 14 unique variants (e.g. missense and frameshift) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. Summary of Case Level Data: 8 POINTS Variants in this gene have been reported in at least 17 probands in over 11 publications (PMIDs: 31285529, 19780765, 28255779, 25033742, 24596948, 15592994, 28454995, 31054490). Variants in this gene segregated with disease in at least 7 additional family members.
The mechanism for disease is homozygous or compound heterozygous loss of function variants (PMID: 31285529).
This gene-disease association is supported by animal models, expression studies, and in vitro functional assays.
In summary, SLC22A25 is definitively associated with autosomal recessive epileptic encephalopathy This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
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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