PMC8636088_01
(A,B) Magnetic resonance imaging of the patient's head (Arrow points to area of subdural effusion). (C) Poband (II-1) is shown. The squares represent the proband, and his father. The circle represents the mother. (D) Sanger sequencing showing two alleles of the proband and his parents, respectively.
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F1
Skull magnetic resonance imaging (MRI) of diffusion-weighted images (DWI) of the genu of corpus callosum and the splenium of corpus callosum presented abnormal high-signal shadow, slightly decreased cerebral white matter, and right frontal-temporal-parietal subdural effusion (Figure 1A). MRI re-examination disclosed a widened extracerebral space of bilateral temporal and parietal lobes (Figure 1B). The pedigree was drawn after obtaining detailed family information (Figure 1C). Sanger sequencing showed that the patient inherited the p.(Gln991His) mutation from his father and the p.(Met610Ile) mutation from his mother, consistent with an autosomal recessive mode of inheritance (Figure 1D).
(A-D) Protein molecular models of wild type (upper) and FRMD4A mutations (lower) by I-TASSER. (E) Conservation analysis of the abnormal variation. Results indicate that both Met610 and Gln991 in the FRMD4A protein are highly conserved between different species.
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F2
WT/MUT FRMD4A proteins to determine the pathogenicity of mutant FRMD4A according to I-TASSER. When amino acid 610 was changed to isoleucine, the side chains of FRMD4A also changed, and they tended to be longer than those of a structure in which amino acid 610 was methionine (Figures 2A,B). The mutated H911 protein had a different side chain than the wild-type protein as a result of an amide glutamine being substituted for a basic amino acid histidine (Figures 2C,D). Both p.(Met610Ile) and p.(Gln991His) mutations of the FRMD4A gene consisted of highly conserved amino acid residues among different species (Figure 2E), indicating their structural and functional importance.