| Autor: |
Wang Song, Wen- Jun Bian, Hua Li, Qing- Hui Guo, Jie Wang, Bin Tang, Jia- Yuan Zhang, Wei Wei, Xiao- Rong Liu, Wei- Ping Liao, Bin Li, Na He |
| Zdroj: |
Journal of Medical Genetics; Sep2024, Vol. 61 Issue 9, p895-903, 9p |
| Abstrakt: |
Background IFIH1 variants have been reported to be associated with immune- related disorders with/ without seizures. It is unknown whether IFIH1 variants are associated with common epilepsy without acquired causes and the mechanism underlying phenotypic variation remains elusive. Methods Trio- based whole- exome sequencing was performed on patients with febrile seizures or epilepsy with antecedent febrile seizures. Previously reported variants were systematically reviewed to investigate genotype- phenotype associations. Results Two de novo heterozygous and three biallelic missense variants were identified in five patients with generalised epilepsy with antecedent febrile seizures. The variants were predicted to be damaging by in silico tools and were associated with hydrogen bonding changes to neighbouring amino acids or decreased protein stability. Patients exhibited an early onset age and became seizure- free with favourable outcome. Further analysis revealed that de novo missense variants located in the Hel region resulted in seizures with multiple neurological abnormalities, while those in the pincer domain or C- terminal domain led to seizures with normal neurodevelopment, suggesting a sub- molecular effect. Biallelic missense variants, which were inherited from unaffected parents and presented low allele frequencies in general populations, were associated with seizures without neurological abnormalities. Truncation variants were related to refractory epilepsy and severe developmental delay, suggesting a genotype- phenotype correlation. IFIH1 is predominantly expressed in the neonatal stage and decreases dramatically in the adulthood, which is consistent with the early onset age and favourable outcome of the patients. Conclusions IFIH1 variants are potentially associated with generalised epilepsy with antecedent febrile seizures. The sub- molecular implication and genotypephenotype association help explain phenotype variations of IFIH1 variants. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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