FIGURE 1

Pedigree and molecular analysis. (A) Pedigree clearly depicts the autosomal recessive mode of inheritance. Squares and circles represent males and females. White symbols represent normal, while black symbols represent affected individuals, respectively. The double line represents the consanguineous union. (B) Picture of the affected individual (V-19) showing developmental delay and bound to a wheelchair. Posteroanterior spinal radiographs demonstrating severe scoliosis. (C) Schematic representation of the VWA8 domains (1905 amino acids). Each contains three predicted ATPase, dynein-related AAA domains (blue) with the second AAA domain-containing an ATPase binding site bounded by the Walker A (first red star) and Walker B (second red star) motifs. VWA8a has a predicted von Willebrand factor type A domain (blue star) at the C-terminus containing a metal ion-dependent adhesion site (MIDAS). (D) Representing partial amino acid sequence of the VWA8 amino acid acids, depicting the conservation of Asp316 amino acid across different species. (E,F) Structural 3D representation of VWA8^Asp316 (wild type) and VWA8^Gly316 (mutated). (G,H) Zoomed cartonic representation of the wild type (VWA8^Asp316) and mutated (VWA8^Gly316) protein structure, showing changes in the bonding and overall structure.