case_images: PMC11059961_01
case_images: (A) Electroencephalogram of patient A with a bipolar montage showed generalized slowness in the background activity, along with abundant multifocal epileptic activity and generalized activity. (B) Electroencephalogram of patient B. Electroencephalogram showing reported generalized slowness of background activity with abundant multifocal epileptic activity, predominantly affecting the posterior regions, consistent with a non-convulsive status epilepticus. (C) Electroencephalogram in normal conditions showed generalized slowness in the background activity, along with abundant multifocal epileptic activity and generalized activity.
case_images: fneur-15-1376643-g001.jpg
case_images: PMC11059961_02_fneur-15-1376643-g001.jpg
case_images: fig1
case_images: The electroencephalogram (Figure 1) reported generalized slowness of background activity with abundant multifocal epileptic activity, predominantly affecting the posterior regions, consistent with a non-convulsive status epilepticus (Supplementary Figure 1).
case_images: PMC11059961_02
case_images: (A) Electroencephalogram of patient A with a bipolar montage showed generalized slowness in the background activity, along with abundant multifocal epileptic activity and generalized activity. (B) Electroencephalogram of patient B. Electroencephalogram showing reported generalized slowness of background activity with abundant multifocal epileptic activity, predominantly affecting the posterior regions, consistent with a non-convulsive status epilepticus. (C) Electroencephalogram in normal conditions showed generalized slowness in the background activity, along with abundant multifocal epileptic activity and generalized activity.
case_images: fneur-15-1376643-g001.jpg
case_images: PMC11059961_02_fneur-15-1376643-g001.jpg
case_images: fig1
case_images: The electroencephalogram (Figure 1) reported generalized slowness of background activity with abundant multifocal epileptic activity, predominantly affecting the posterior regions, consistent with a non-convulsive status epilepticus (Supplementary Figure 1).
case_images: Family pedigree. The father had migraine and memory impairment during adolescence. Relatives from the father side have seizures.
case_images: fneur-15-1376643-g002.jpg
case_images: PMC11059961_02_fneur-15-1376643-g002.jpg
case_images: fig2
case_images: Additionally, two female and two male cousins from the patient's father's side have presented with seizures but without any other accompanying neurological symptoms (Figure 2). The nonsense variant has a frequency of 0.00002368 in The Genome Aggregation Database (gnomAD version V2.1.1). The variant was heterozygous in the sisters and the father, not in the mother. Algorithm developed to predict the effect of missense changes on protein structure and function result in the following: PolyPhen-2: "Damaging" (0.981). The amino acid residue arginine is found in multiple mammalian species, suggesting that this missense negatively affects the function of the protein (Supplementary Figure 2).
case_images: (A,B) Cartoon representations illustrate the protein structures of both CACNA1A wild-type (wt) and the R2467P mutant. The structures are color-coded by secondary elements: white represents loops, green indicates helices, and purple denotes sheets. On the left (blue arrow) is the wt structure, featuring the polar residue arginine. On the right (red arrow) is the R2467P mutant, characterized by the non-polar residue proline. (C,D) Surface representations depict the protein structures of both CACNA1A wild-type (wt) and the R2467P mutant. The structures are color-coded based on electrostatic values: red represents negative values (-10 min), white corresponds to 0, and blue signifies positive values (10 max). On the left (within the yellow oval) is the wt structure, featuring the polar residue arginine. On the right (within the green oval) is the R2467P mutant, characterized by the non-polar residue proline. Note the discernible modification in the electrostatic surface of this Intrinsically Disordered Region (IDR) caused by the mutation. (E) STRING network analysis of CACNA1A reveals a comprehensive interaction network involving proteins associated with its interaction. The connections are highlighted by co-expression (black), text mining (green), protein homology (purple), and experimentally determined interactions (pink).
case_images: fneur-15-1376643-g003.jpg
case_images: PMC11059961_02_fneur-15-1376643-g003.jpg
case_images: fig3
case_images: This mutation changes residue 2,467 from a polar amino acid (arginine) to a non-polar proline with an amide lateral chain, impacting electron interaction, as seen in Figures 3A-E.