BDNF N187S and M189T variants influence platelet function. (A) Modeled structure of BDNF and NT4. BDNF is represented in green and NT4 in orange. The arrows represent the B-strands, and the coiled regions are represented by the thin lines. N187S and M189T are indicated on the 3D structure of BDNF and are located on loop III. (B) Family trees of the 2 families carrying the rare BDNF variants. (C) Immunoblotting of BDNF in platelet lysates of the 2 ASD families; 50 µg of protein was loaded in each well, and 2 healthy volunteers were used as controls. Integrin β3 was used as a loading control. For carriers of BDNF N187S variant, traces of platelet aggregation in response to 0.25 µg/mL and 1 µg/mL collagen are shown, as well as ATP release in response to 2 µg/mL collagen (D). (E) Traces of platelet aggregation as well as ATP release in response to 10 µM of ADP. For carriers of BDNF M189T variant, traces of platelet aggregation in response to 0.25 µg/mL and 1 µg/mL collagen are shown, as well as ATP release in response to 2 µg/mL collagen (F). (G) Traces of platelet aggregation as well as ATP release in response to 10 µM of ADP. The green band corresponds to the local normal reference range for ATP secretion (n = 40). Participants are color-coded; their maximal platelet aggregation (%) in platelet-rich plasma is indicated in the legend.