case_images: PMC9888409_01
case_images: (A) Pedigree of the investigated family. (B-E) MRI and radiographs of the proband showing platybasia at the skull base, delayed myelination for the patient's age, and severe skeletal deformities. (F,G) Sanger sequencing electrograms of the proband and wild-type. (H) Schematic diagram of the TBX2 protein showing the position of the identified variant. (I) Partial amino acid sequence of the TBX2 protein showing conservation of Lys177 across different species. (J, K) Mutational and structural analyses of TBX2. Structural differences between (J) TBX2WT (coral) and (K) TBX2LYS177TER (sea green). All the secondary structures, N-terminal, and C-terminal are labeled in black color. Lys177 is shown and labeled in red color.
case_images: fgene-13-1117500-g001.jpg
case_images: PMC9888409_01_fgene-13-1117500-g001.jpg
case_images: F1
case_images: The proband (II-1) had the clinical features such as chondrodysplasia, short stature, and global developmental delay (Figure 1A). There was occurrence of platybasia at the skull base, and delayed myelination for the patient's age was observed (Figure 1B). The liver, spleen, pancreas, and adrenals were unremarkable (Figures 1B-E). All these skeletal changes favor the chondrodysplasia punctata type of skeletal dysplasia (Figures 1B-E). TBX2 gene (c.529A>T; p.Lys177*; NM_005994.4) was detected which was validated by Sanger sequencing (Figures 1F, G). The variant had a The Lys amino acid at position 177 was highly conserved across different species (Figures 1H, I). TBX2LYS177TER), and the alpha11 region was extended from Lys166 to Ala175 (Figures 1J, K). These structural changes were unique to TBX2LYS177TER and were not present in TBX2WT.
case_images: Time-dependent RMSD, RMSF, and Rg analyses of TBX2WT and TBX2LYS177TER over the 100 ns simulation time. (A, B) RMSD plot over the function of time. (C, D) RMSF plot over the function of time. (E, F) Radius of gyration plot over the function of time. TBX2WT is depicted in coral, while TBX2LYS177TER is depicted in sea green color. (G, H) Conformational changes in TBX2WT and TBX2LYS177TER over the 100 ns simulation time. (G) Conformational changes in TBX2WT at 0 and 100 ns. (H) Conformational changes in TBX2LYS177TER at 0 and 100 ns. TBX2WT is depicted in coral, and TBX2LYS177TER is depicted in sea green color. The black dotted lines signify the cavities. N- and C-terminals are depicted in black color.
case_images: fgene-13-1117500-g002.jpg
case_images: PMC9888409_01_fgene-13-1117500-g002.jpg
case_images: F2
case_images: As a result of this interaction, TBX2WT assumes a circular shape, with the inner side forming a circular cavity (as depicted in Figures 2G, H).