Figure 1

Clinical and laboratory phenotype of the index case. Pedigree (A) showing the index case (P1; shaded) who displayed reduced skin, hair and iris pigmentation (B). Whole blood lumiaggregometry (C) was performed on EDTA-anticoagulated blood from P1 and from a healthy control (HC) using the activating agonists collagen (5 μg/ml) and ADP (10 μM). In the top panel, platelet aggregation is indicated by change in electrical impedance after addition of the agonist. In the bottom panel, platelet dense granule release is indicated by ATP secretion. Lytic granule release from lymphocytes from P1 (D) was measured by determining the increase in the percentage of CD107a positive cytotoxic T-lymphocytes CTL (top panel) and natural killer (NK) cells (bottom panel) after stimulation with phytohaemagglutinin and anti-CD3 respectively. Data are also presented from 39 healthy controls with the median control value indicated by the horizontal line. Expression of AP-3 β3A was determined in P1 by immunoblotting protein extract from EBV-immortalised B-lymphoblastoid cells using an anti-β3A subunit antibody (E). Control data are presented from a healthy control (HC) and from an unrelated individual with genetically confirmed HPS2 (HPS2). Control experiments were performed using an anti-GAPDH antibody. Migration of relevant molecular mass protein markers are indicated on each immunoblot.