Figure 1.

Pedigree phenotype. (A) Pedigree of the affected family, in which black, white and grey symbols indicate presence of the bleeding phenotype, absence of the bleeding phenotype and unknown bleeding phenotype, respectively. The genotype, where known, is shown under each symbol, where G is the mutant allele and C is the reference allele. Double lines indicate consanguinity and strike-through lines are used to indicate deceased individuals. (B) Human Phenotype Ontology (HPO) annotation of the three affected family members. (C) A ribbon diagram of the crystal structure of aspirin-acetylated cyclo-oxygenase 1 (COX-1) showing the location of the variant for the proband which results in a missense substitution of tryptophan to serine at amino acid 322.