case_images: PMC11803908_01
case_images: Clinical and genetic findings. (A) Frontal and lateral view of the facial features of patient 1, showing broad forehead, triangular face, down-slanting palpebral fissures, exotropia, mandibular hypoplasia with pointed chin, and low-set ears. (B) Patient 2 showing dysmorphic features: Mild epicanthus, short nose with flattened nasal bridge, slightly anteverted nares, and mandibular hypoplasia with pointed chin. (C) EEG showing disorganized posterior rhythm with superimposed slow anterior activity and high-voltage bilateral spikes, polispikes, and sharp waves, predominantly over the temporal and central regions, enhanced during sleep. (D) Linear structure of the RALA protein, showing the GTP/GDP-binding regions (GBR), effector region (ER), effector domain (ED), and post-translational modification regions (PTM). The GBR is essential for the protein's molecular switch activity, while the ER and ED mediate interactions with downstream effectors. PTMs regulate protein activity, localization, and interactions. Variants identified in our patients and in prior studies are highlighted to illustrate their positions within these functionally critical regions.
case_images: MGG3-13-e70072-g001.jpg
case_images: PMC11803908_01_MGG3-13-e70072-g001.jpg
case_images: mgg370072-fig-0001
case_images: An ophthalmological examination revealed alternating exotropia, treated with occlusions (Figure 1A). Physical examination showed dysmorphic facial features, including mild epicanthus, a short nose with a flattened nasal bridge and slightly anteverted nares, mandibular hypoplasia with pointed chin (Figure 1B). Electroencephalograms (EEGs) showed a disorganized posterior rhythm with superimposed slow anterior activity and high voltage bilateral spikes, polyspikes and sharp waves especially over the temporal and central regions enhanced by sleep (Figure 1C). Brain MRI revealed enlargement of pericerebral frontal and temporal spaces (Figure S1). This variant is absent in gnomAD and affects a highly conserved residue in close proximity with a GTP/GDP binding site (amino acidic residues 70-71, Figure 1).