case_images: PMC10597645_01
case_images: The clinical data of the family with epilepsy and/or myoclonus. (A) Pedigree figure. Family members are identified by generations and numbers. Squares indicate male family members; circles, female members; closed symbols, the affected members; open symbols, unaffected members; arrow, proband. (B) 24 h of video scalp EEG monitoring showed diffuse spike waves during the interictal period. (C) Synchronized surface EMG showed spikes when the patient has myoclonic seizures. (D) Synchronized surface EEG showed spikes when the patient has myoclonic seizures. (E) Patient's handwriting showed tremor-like movement before and after STN-DBS treatment.
case_images: fgene-14-1208540-g001.jpg
case_images: PMC10597645_01_fgene-14-1208540-g001.jpg
case_images: F1
case_images: A two-generation Han Chinese pedigree, comprising six members, was recruited for this study (Figure 1A). S1, after deep brain stimulation (DBS) of the subthalamic nucleus (STN) treatment). Scalp electroencephalogram (EEG) monitoring conducted over a 24-h period revealed diffuse spike waves during the interictal period (Figure 1B). Spikes (deltoid and thenar muscles) were observed on synchronized surface electromyography (EMG) recordings (Figure 1C), and epileptiform discharges linked to EMG spikes were found on synchronized EEG recordings (Figure 1D). The myoclonic tremor symptoms in this patient improved postoperatively, and the epilepsy was well controlled with the above-mentioned antiepileptic drugs (Figure 1E).
case_images: The genetic analysis of family. (A) Schematic representation of the filter strategies employed in our study. (B) Sanger sequencing of DHDDS confirmed the mutation (NM_001243564.1, c.113G>A/p. R38H) in II-1 and III-1. Arrow indicates the c.113G site. (C) Alignment of multiple DHDDS protein sequences across species. The R38H affected amino acid locates in the highly conserved amino acid region in different mammals (from Ensembl). Letters in red show the R38 site. (D) The part structure of WT and mutated DHDDS protein. Red squares represent R38 site.
case_images: fgene-14-1208540-g002.jpg
case_images: PMC10597645_01_fgene-14-1208540-g002.jpg
case_images: F2
case_images: After data filtering (Figure 2A), 11 mutations were detected following public database filtering, bioinformatic program prediction, and family cosegregation analysis (Table 1). Sanger sequencing confirmed that this mutation was present in the proband and his mother but absent in his father (Figure 2B). This rare mutation resulted in the substitution of arginine with histidine and was located at a highly evolutionarily conserved site (Figure 2C). R38H) altered the polarity of the protein, which may further affect the protein function of DHDDS (Figure 2D).