case_images: PMC11782219_01
case_images: Patient history timeline. In the diagram, the light blue thick arrows represent the treatment timeline, and the dark blue arrows represent the key time points. The upper part of the arrows indicates clinical symptoms and tests, while the lower part indicates genetic diagnosis and treatment measures.
case_images: fgene-15-1508922-g001.jpg
case_images: PMC11782219_01_fgene-15-1508922-g001.jpg
case_images: F1
case_images: A timeline of the patient's medical history is shown in Figure 1.
case_images: Pedigree and Sanger sequencing chromatograms of the identified variant. (A) Schematic presentation of the familial pedigree of the patient. White fill represents an unaffected family member, while black fill represents an affected member. (B) Sanger sequencing chromatogram of RORB in the family. The variant c.94-1G>A in RORB was heterozygote in the patient, mosaic in the father, and not found in the mother.
case_images: fgene-15-1508922-g002.jpg
case_images: PMC11782219_01_fgene-15-1508922-g002.jpg
case_images: F2
case_images: Brain MRI was normal (Supplementary Figure S2), while EEG findings were abnormal: intermittent spikes and slow waves with moderate amplitude were observed in the right central and anterior temporal regions during wakefulness (Supplementary Figure S3).
case_images: Minigene assay analysis of the RORB variant c.94-1G>A. (A, B) pcMINI (A) and pcMINI-C (B) vector used for minigene analysis. The left side shows a schematic diagram of the minigene vector construction. In the middle are the RT-PCR detection results of bands harboring spliced transcripts product in MCF-7 and 293T cells. On the right are the sequencing results of the bands harboring spliced transcripts product. a for wild type, b for mutant. (C) RORB amino acid sequence comparison between wild type and mutant. The blue box represents the C4-type ZnF domain and the green box represents the LBD domain (C-terminal ligand binding domain).
case_images: fgene-15-1508922-g003.jpg
case_images: PMC11782219_01_fgene-15-1508922-g003.jpg
case_images: F3
case_images: Brain MRI was normal (Supplementary Figure S2), while EEG findings were abnormal: intermittent spikes and slow waves with moderate amplitude were observed in the right central and anterior temporal regions during wakefulness (Supplementary Figure S3).
case_images: Summary of the pathogenic or likely pathogenic variants of RORB. There were 33 cases of pathogenic or likely pathogenic RORB gene variations, 11 in the C4-ZnF domain, 14 in the LBD domain, and 9 in other non-functional domains. Red indicates the likely pathogenic variant identified in this study.
case_images: fgene-15-1508922-g004.jpg
case_images: PMC11782219_01_fgene-15-1508922-g004.jpg
case_images: F4
case_images: During wake-sleep transitions, scattered, paroxysmal, and continuous low-to-moderate amplitude spikes and spike-slow waves were noted in the right central, parietal, posterior temporal, bilateral occipital, and parietal midline regions, with increased frequency during sleep (Supplementary Figure S4).