MDN1 variants cause susceptibility to epilepsy

Figures

• 

  Fig. 1. Genetic data of cases with MDN1 variants. a Pedigrees of the five cases with MDN1 variants and their corresponding phenotypes. b DNA sequence chromatograms of the MDN1 variants. Arrows indicate the positions of the mutations

• 

  Fig. 2. Representative EEGs and MRI of patients with MDN1 variants. a Interictal EEG of Case 2 showed spike waves in the right parieto-occipital region at the age of 8 years. b Interictal EEG of Case 4 showed spikes and spike-slow waves in the bilateral frontal, central, and midline regions at the age of 9 years. c The MRI of Case 4 showed cortical atrophy and encephalomalacia in the bilateral frontal and parietal lobes

• 

  Fig. 3. Schematic illustration of variant locations, hydrogen bond changes, and hydrophobicity alterations. a Linear schematic of missense MDN1 variants and their locations on the MDN1 protein. Variants identified in this study are shown above; variants identified in the control cohort are shown below. b Changes of hydrogen bonds and free energy change value (*DDG, kCal/mol) of the missense variants. The red dotted line represents hydrogen bonds. The red arrow indicates the change in hydrogen bonds. c Fauchère and Pliska hydrophobicity scale illustrates the hydrophobicity of 20 amino acids. Abscissa: from left to right, hydrophobicity gradually decreases. Blue amino acids are hydrophobic, green amino acids are neutral, and yellow amino acids are hydrophilic. Amino acids with high positive values are more hydrophobic, whereas amino acids with low negative values are more hydrophilic. d The variant characteristics of each case. Each alteration was assigned 1 point; variants in splice sites that may affect protein length were assigned 5 points. One " + " represents 1 point. Abbreviations: CPS, Complex partial seizure; FS, Febrile seizure; FS + , Febrile seizures plus; GTCS, Generalized…

• 

  Fig. 4. Genetic-dependent (expression) stage of MDN1. a RNA expression of MDN1 in normal adult tissues. b Temporal expression of MDN1 in various brain regions. Curves represent the temporal expression patterns of MDN1 in different brain areas. The expression levels were retrieved from the human RNA-seq data in the BrainSpan database. The curve was fitted via the locally weighted scatterplot smoothing (LOWESS) method. Abbreviations: RPKM, Reads per kilobase per million mapped reads