PMC9366085_01
Brain magnetic resonance (MR) images of the patients. (A-D) and (E-H) show scattered high signal intensity in the bilateral frontal and parietal periventricular white matter.
fneur-13-928334-g0001.jpg
PMC9366085_01_fneur-13-928334-g0001.jpg
F1
Magnetic resonance imaging (MRI) revealed scattered high signal intensity in the bilateral frontal and parietal periventricular white matter (Figure 1).
An electroencephalogram (EEG) shows diffuse slow wave activity with mainly 2-4 Hz moderate- and high-potential delta/theta activity, approximately symmetrical.
fneur-13-928334-g0002.jpg
PMC9366085_01_fneur-13-928334-g0002.jpg
F2
An electroencephalogram (EEG) showed diffuse slow wave activity with mainly 2-4 Hz moderate- and high-potential delta/theta activity, approximately symmetrical (Figure 2).
The gene variations were validated using Sanger sequencing.
fneur-13-928334-g0003.jpg
PMC9366085_01_fneur-13-928334-g0003.jpg
F3
The gene variations were validated using Sanger sequencing (Figure 3).
Conservation of the identified amino acids across diverse species (A, D) and the 3D modeling for the IVD-wild and identified missense variant of site 75 (B, C) and site 399 (E, F) in our patient with isovaleric acidaemia (IVA).
fneur-13-928334-g0004.jpg
PMC9366085_01_fneur-13-928334-g0004.jpg
F4
The conservation of the identified amino acids across multiple species and the 3D protein modeling of the variants are shown in Figure 4.
Distribution of the isovaleryl-CoA dehydrogenase (IVD) variants. Blue: the alpha-helical N-terminal domain and the second alpha-helical C-terminal domain of IVD; yellow: the beta-sheet domain; and gray: intron region. Numbers represent the corresponding amino acid sites.
fneur-13-928334-g0005.jpg
PMC9366085_01_fneur-13-928334-g0005.jpg
F5
As illustrated in Figure 5, pathogenic variants were non-uniformly distributed along the IVD sequence.
Cumulative distribution of the IVD variants, comparing variant distribution in symptomatic patients (including, acute neonatal and chronic intermittent type) with that of asymptomatic patients (A), and the acute neonatal type vs. the chronic intermittent type (B). Green striped boxes: FAD binding sites. FAD, flavin adenine dinucleotide.
fneur-13-928334-g0006.jpg
PMC9366085_01_fneur-13-928334-g0006.jpg
F6
Figures 6A,B shows the cumulative distribution of symptomatic patients (including acute neonatal and chronic intermittent types) and asymptomatic, acute neonatal, and chronic intermittent patients, respectively. In Figure 6A, three steep regions were revealed: (a) 123-159; (b) 282-318; and (c) 356-403. In Figure 6B, two steep areas can be observed: (a) 123-159 and (b) 356-403.
Three-dimensional (3D) modeling of areas 123-159 and 356-403. (A) Yellow: the 123-159 region; green: FAD; blue: CoA Persulfide; purple: FAD binding sites (numbered). (B) Yellow: the 356-403 region; green: FAD; blue: CoA Persulfide; yellow balls: FAD binding sites (numbered). FAD, flavin adenine dinucleotide.
fneur-13-928334-g0007.jpg
PMC9366085_01_fneur-13-928334-g0007.jpg
F7
The 3D modeling and conservation of amino acid sequences among different species in areas 123-159 and 356-403 are shown in Figures 7, 8, respectively.
Conservation of amino acid sequences in areas 123-159 and 356-403 across diverse species.
fneur-13-928334-g0008.jpg
PMC9366085_01_fneur-13-928334-g0008.jpg
F8
The 3D modeling and conservation of amino acid sequences among different species in areas 123-159 and 356-403 are shown in Figures 7, 8, respectively.
The IVD variant distribution in Chinese patients with IVA.
fneur-13-928334-g0009.jpg
PMC9366085_01_fneur-13-928334-g0009.jpg
F9