Mutacje genu HIVEP3 mogą być związane z epilepsją

PURPOSE: The HIVEP3 gene encodes a zinc finger protein that regulates nuclear factor κB-mediated transcription and plays an essential role in neurodevelopment. Its association with human disease remains elusive. METHODS: Trio-based whole-exome sequencing was performed in patients with unexplained epilepsy. Genotype-phenotype correlation and protein-protein interactions were analyzed to reveal gene-disease association. RESULTS: We identified six biallelic HIVEP3 missense variants in six unrelated cases, including one familial and four sporadic cases with mild epilepsy and one sporadic case with epilepsy and developmental disorders. These variants showed significantly lower minor allele frequencies than benign variants. Further analyses revealed a higher proportion of missense variants in the epilepsy group than in the neurodevelopmental disorders group; a correlation between phenotype severity and damaging degree of the variants; and high HIVEP3 expression in the brain consistent with onset ages of the patients. Protein-protein interaction analysis identified nine HIVEP3-interacting proteins associated with epilepsy and neurodevelopmental disorders. CONCLUSION: HIVEP3 variants are potentially associated with epilepsy. The gene-disease association is supported by genotype-phenotype correlations, damaging effects of the identified variants and their correlated phenotypes, as well as spatiotemporal expression patterns of HIVEP3.