Patient with JAK2R564Q mutation displays MPN. (A) Examination of the index patient's blood smear revealed increased platelet number. Platelet morphology and granulation were normal, and most platelets were of normal size (black arrows). Rarely, however, giant platelets were observed (open arrow). (B) Sequence analysis revealed a novel G-to-A single-point mutation in JAK2 at nucleotide 1691, causing an amino acid substitution of arginine for glutamine at position 564 (C). (D) Pedigree of the studied ET family. Squares represent males, circles represent females. JAK2R564Q-positive family members are shown in black, and the JAK2R564Q-negative member in white. Plts indicates platelet counts of each family member (×103/μL). (E) Alignment of JAK2 sequences from different species shows that the arginine at position 564 in the pseudokinase domain is highly conserved. (F) Three-dimensional model of the JAK2 JH2 pseudokinase domain based on Bandaranayake et al16 with the N lobe colored orange and the C lobe colored blue. Arginine 564 (R564) is located in the 5 stranded β sheet of the N lobe.
