Identification of GNE compound heterozygote variants in a patient with macrothrombocytopenia. (A) Representative images of Giemsa staining of peripheral blood smears from the patient (age 16), the patient’s father (age 40), and a healthy individual (age 28) as normal control who has no family relationship with the patient or his other family members. The size of patient’s platelets was nearly 3 times larger than that of the normal control. Arrows indicate enlarged platelets. Arrowheads indicate normal platelets. Black boxes indicate platelets with higher magnification. Scale bar, 10 μm. (B) Genomic DNA sequences of exon 10 and exon 12 of GNE in father- and patient-derived blood cells. Letters and numbers in red indicate mutated residues and sites in the GNE protein sequence, respectively. (C) Pedigree of the family. The filled square indicates the patient, who is the proband, and the half-filled square and circle indicate heterozygous father and mother, respectively. (D) Schematic domain structure of GNE carrying combined missense mutations in the patient. (E) MFI of MAL-II and platelet surface marker CD42a on peripheral platelets from the patient, patient’s father and a healthy individual as normal control (the same individual as in Figure 1A), respectively. MFI, mean fluorescence intensity; FSC, forward scatter; MAL-II, Maackia amurensis lectin II, binds to α-2,3 linked sialic acid. ∗P < .05; ∗∗∗P < .001.