Abstract
The fast pace of gene discovery has resulted in groundbreaking advances in the field of epilepsy genetics. Clinical testing using comprehensive gene panels, exomes, or genomes is now increasingly available and has significantly increased the diagnostic yield for early-onset epilepsies and enabled precision medicine approaches. In this paper, we report a case of epilepsy in a pedigree. The proband had heterozygous mutations in KCNC1 (NM_001112741.1:c.959G>A, p. Arg320His), CAPN3 (NM_000070.2:c.526G>A, p. Val176Met), and NEFH (NM_021076.3:c. 2595 delC, p. Lys866Argfs*51). Sanger sequencing verification was consistent with the results of whole-exome sequencing. The KCNC1 mutation was a de novo mutation, and the CAPN3 and NEFH mutations were inherited from their father and mother, respectively. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, a heterozygous mutation was found for APOB (NM_000384.2: c.10579C > T, p. Arg3527Trp). The heterozygous mutation at this site was inherent in the pedigree. Coexpression analysis indicated that heterozygous mutations of KCNC1, CAPN3, NEFH, and APOB were closely related to the clinical phenotypes of the patient, and the clinical phenotypic heterogeneity of the disease may be the result of the interaction of multiple genes.
Highlights
Epilepsy is a disorder of the central nervous system caused by abnormal discharge of neurons that affects consciousness, sensation, temperament, and movement
The classification levels of epilepsy diagnosis are based on seizure type, epilepsy type and epilepsy syndrome, and 40% of epilepsy is related to genetic factors [1–4]
A protein–protein interaction analysis was performed on the following targeted genes and their interacting genes: KCNC1, CAPN3, NEFH, and APOB; the results indicated that the proteins were highly interacting (Figures 2, 3), suggesting that the combination of heterozygous mutations in multiple genes led to a severe phenotype
Summary
Epilepsy is a disorder of the central nervous system caused by abnormal discharge of neurons that affects consciousness, sensation, temperament, and movement. The classification levels of epilepsy diagnosis are based on seizure type, epilepsy type (focal, generalized, combined generalized and focal, and unknown) and epilepsy syndrome, and 40% of epilepsy is related to genetic factors [1–4]. More than half of active epilepsy cases are 12 years old. The clinical features of epilepsy are complex and diverse and can manifest as paroxysmal movement, abnormal autonomic nerve function, transient sensory disorders, limb convulsions, loss of consciousness, and mental disorders. The etiology of epilepsy is heterogeneous and includes genetic factors, brain diseases, and systemic diseases. An imbalance between excitation and inhibition of the central nervous system leads to epileptic attack, and ion-channel
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
