case_images: PMC11402803_01
case_images: Imaging features of proband II & III. (A) Brain magnetic resonance imaging (MRI) displayed small focal signal abnormalities in the bilateral occipital lobes in proband II. (B) Brain MRI showed slightly thinner genu and splenium of the corpus callosum along with irregular bilateral lateral ventricles, mildly enlarged posterior horn, and widened left temporal subarachnoid space in proband III.
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case_images: PMC11402803_01_fgene-15-1382275-g001.jpg
case_images: F1
case_images: Electroencephalogram (EEG) demonstrated moderate abnormal electrical activity, whereas brain magnetic resonance imaging (MRI) displayed small focal signal abnormalities in the bilateral occipital lobes (Figure 1A). MRI showed slightly thinner genu and splenium of the corpus callosum along with irregular bilateral lateral ventricles, mildly enlarged posterior horn, and widened left temporal subarachnoid space (Figure 1B).
case_images: Genetic information of three families. (A-C) is the pedigree and sanger sequencing chromatogram of proband I, II & III, respectively.
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case_images: PMC11402803_01_fgene-15-1382275-g002.jpg
case_images: F2
case_images: Proband I: c.489dup (p.Gly164fs*) inherited from the mother and c.1897C>T (p.Arg633Trp) inherited from the father; Proband II: c.2314C>T (p.Arg772*) inherited from the father and c.5002T>A (p.Tyr1668Asn) inherited from the mother; Proband III: c.5113G>T (p.Val1705Phe) inherited from the father and c.718delG (p.Glu240fs*) inherited from the mother, respectively (Table 1; Figure 2).
case_images: Nucleic acid and amino acid information of the variants. (A) Conservation analysis of the three missense variants. *: Highly conserved in multiple species. The red background shows the variant amino acid sequence information. (B) Local diagram of the number of hydrogen and clasher bonds changed in ASCC3 homologous protein (NM_006828). Variation: p.Y1668N, the hydrogen bond disappeared before (top) and after (bottom) variation; p. R633W and p.V1705F, although the hydrogen bonds were not changed before and after the variation, the side-chain r group was mutually exclusive with other amino acid atoms (purple), which may affect the correct folding of their active conformation. (C) All the variation information of ASCC3 variations causing neurodevelopmental disorders, and the red background is the variation found in this study.
case_images: fgene-15-1382275-g003.jpg
case_images: PMC11402803_01_fgene-15-1382275-g003.jpg
case_images: F3
case_images: The three reported missense variations all occurred at highly conserved amino acid positions (Figure 3A). These alterations have the potential to impact the functional characteristics of the protein (Figure 3B). ASCC3 variants associated with autosomal recessive mental developmental disorder 81 (MIM: 62070). Among them, missense mutation (10), frameshift mutations (4), nonsense mutations (3), splice site mutation (1), and highlighted in this paper are those carried by patients indicated with a red background (Figure 3C).