Genetic and structural information and relation with phenotype. (A) Pedigree showing affected (filled) and nonaffected (open) females (circles) and males (squares). The propositus (ii.4) is indicated by an arrow. Platelet counts (× 10⁹/L) and the genotypes for the 2 nsSNPs (nucleotide 206 in GP1BA and 2245 in ITGB3) are given for each member tested (heterozygotes in bold). Where data are lacking, samples were either not available or not tested (n.t.). (B) Top panel shows position of the GP1BA and ITGB3 genes on chromosome 17 (indicated by red boxes). Middle panels show the DNA sequencing traces in the propositus and a control show heterozygous calls (N) at nucleotides 206 and 2245 in the GP1BA and ITGB3 genes, respectively. In the bottom panel, the nucleotides and corresponding amino acids are indicated. The 2 mutations 206C>T and 2245G>C and the amino acid replacements L53P and D723H are presented in red. (C) Ribbon diagram of the VWF (green) and GPIbα (blue) complex based on the crystal structure,¹⁶  which shows residue 53 (red ball) on the convex, non–ligand-facing surface of GPIbα. (D) Modeling of the D723H mutation onto the Nuclear Magnetic Resonance (NMR) structure¹⁷  of the membrane proximal segment of the cytoplasmic tails of α_IIb and β₃. top panel show β₃ as a yellow ribbon with side chains showing and a space-filling model of α_IIb with the surface colored according to charge, with red indicating negative and blue indicating positive. The overall change in the electrostatic surface potential caused by the D723H mutation is illustrated in the 2 space-filling models of β₃ in the bottom panel with wild-type at the left and mutant at the right showing the loss of negative charge in the mutant. Structural figures were generated using the program Pymol. (DeLano Scientific, Palo Alto, CA).