PRIMA1 was first reported in relation to autosomal recessive epilepsy in 2015 (Hildebrand et al., PMID: 26339676). The publication includes two affected adult siblings from a single family with sleep-related hypermotor epilepsy, intellectual disability, ataxia, and cerebellar hypoplasia. A single splice site variant has been reported in both siblings and was noted to result in skipping of exon 2 (the first coding exon), leading to reduced AChE (acetylcholinesterase) at the synapse causing acetylcholine accumulation and an enhanced cholinergic response (PMID: 26339676). There is currently no additional clinical or functional evidence available for PRIMA1 in association with epilepsy.
In summary, there is limited evidence to support the relationship of PRIMA1 to autosomal recessive epilepsy. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Epilepsy GCEP on January 7, 2025 (SOP Version 11).
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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