PMC9578642_01
Growth charts of the patient. (A) Z-score for length (red dot) and weight-for-length (blue cross) at 0-2 years of age. (B) Z-score for height (red dot) and weight-for-height at 1-16 years of age. Growth hormone (GH) therapy was started at 3 years of age.
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F1
Figure 1 presents the growth charts of the patient.
(A) Schematic structure of the original and the mutant amino acid. (B) Overview of the protein in ribbon-presentation. The protein is coloured by element; alpha-helix = blue and random coil = cyan. (C) Close-up of the mutation. The protein is coloured grey, the side chains of the wild-type (green) and the mutant residue.
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F2
Analysis of the mutant protein by HOPE showed that the mutant residue is bigger, more hydrophilic and introduces a positive charge compared to the smaller, neutral charged wildtype residue (Figure 2).
(A) Chromatograms of direct sequence analysis of IGF2 gene showing the missense variant c.122T > G, p.Leu41Arg in the patient (B) the SNP rs3213225 in the patient and father (C) IGV view of the patient's sequence data shows that the reads with SNP alternative allele A (in green) and the missense variant c.122T > G (in blue) are on different reads. The father is heterozygous (G/A) for the SNP and the mother is homozygous (A/A). The reads with the SNP reference allele G, that also carry the missense variant c.122T > G, must be paternal.
fped-10-969881-g003.jpg
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F3
The IGF2 missense variant was confirmed by Sanger sequencing and was absent in the parents (Figure 3A). The child and father were heterozygous (G/A) for the SNP and the mother was homozygous (A/A) (Figure 3B). By exploring the reads in the Integrative Genomics Viewer (IGV), we found that the reads with SNP reference allele G also carried the missense variant indicating that the missense variant occurred on the paternal allele (Figure 3C).