PRICKLE1 was first reported in relation to autosomal recessive progressive myoclonic epilepsy (PME) in 2008 when Bassuk et al. studied 3 large consanguineous Middle Eastern pedigrees with autosomal recessive PME without variants in CSTB, another gene associated with Unverricht-Lundborg syndrome (PMID: 18976727). These families were all found to have an identical homozygous p.Arg104Gln variant. Later in 2018, Mastrangelo M et al. identified another proband with a similar phenotypic presentation and the homozygous p.Ala274Thr variant (PMID: 30345727). Additional probands were identified in the literature; however, they were not scored based on atypical phenotypes not consistent with PME and the high minor allele frequency of the variants detected (PMID: 30564977, 37593999). Per criteria outlined by the ClinGen Lumping and Splitting guidelines, we found a difference in inheritance pattern and phenotypic variability. Therefore, the following disease entities have been split into two disease entities: autosomal recessive progressive myoclonic epilepsy (PME) and autosomal dominant epilepsy. The split curation for autosomal dominant epilepsy has been curated separately. Experimental evidence identified in the literature was not scored as it did not provide sufficient evidence supporting the gene-disease relationship.
In summary, there is limited evidence to support the relationship between PRICKLE1 and autosomal recessive progressive myoclonus epilepsy (PME). This classification was approved by the ClinGen Epilepsy GCEP on the meeting date July 1, 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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