PMC6446253_01
(A) Front and (B) side views of the patient at 1 year and 9 months of age. Brain MRI at 1.5 months of age showed (C) slight dilatation of the lateral ventricles, mildly hypoplastic inferior vermis and (D) dilated fourth ventricle. (E) An electropherogram of the genomic DNA sequence of the patient showed a de novo duplication in CHD7: c.6341_6358dup (Asp2119_Pro2120ins6) A mutated sequence with duplication in red written beneath. (F) Alignment of CHD7 protein fragment for 9 different placental mammal species confirmed that the Asp2119_Pro2120ins6 non-frameshift insertion affects an evolutionary conserved region. Secondary structures of the peptide encoded by the wild type (left) and Asp2119_Pro2120ins6 mutated (right) exon 31 of CHD7 are shown as rainbow ribbons. (G) The new short alpha helix that is formed by the inserted amino acid residues is in yellow. Models of wild-type and mutated protein structure were formed using SWISS-MODEL software. MRI indicates magnetic resonance imaging.
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PMC6446253_01_10.1177_1178631019839010-fig1.jpg
fig1-1178631019839010
Figure 1A and B) is the firstborn male child of healthy non-consanguineous parents. Family history was unremarkable, with no undue exposure to teratogens reported. A brain magnetic resonance imaging (MRI) examination performed at 1.5 months of age showed mildly hypoplastic inferior vermis, slight dilatation of the lateral ventricles, and dilated fourth ventricle (Figure 1C and D). MIM 214800) confirmed by Sanger sequencing (Figure 1E), which affects an evolutionary constrained region (Figure 1F). Modelization of the putatively encoded mutated protein suggests that the insertion of this chain of 6 amino acid residues potentially substitutes a linear chain into a short alpha helix (Figure 1G).