PMC7174646_01
Characteristics of the peripheral blood and bone marrow of the THC2 proband. The peripheral blood smear (A) and the bone marrow aspirate smear (B) were stained with May-Grunwald-Giemsa. The bone marrow biopsy was stained Hematoxylin and eosin (C) and anti-CD61 staining (D). Scale bars represent 10 mum.
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F1
Her peripheral blood smear showed target cells, teardrop cells as well as schistocytes of red blood cells, and confirmed low platelet count with variable platelet size (Figure 1A). Her bone marrow aspirate smear and biopsy showed increased erythropoiesis, increased leukocytopoiesis and increased megakaryocyte number with hypolobulated nuclei (Figures 1B-D).
Genetic profile, pedigree, laboratory and clinical characteristics of the THC2 family. (A) The linkage analysis including 16 family members was performed with Affymetrix Genome-wide Human SNP 6.0 under a completely penetrant autosomal-dominant model with a disease allele frequency of 0.0003. (B) Mutation c.-128G > T in the 5' UTR of ANKRD26 was confirmed by Sanger sequencing. (C) The pedigree of the THC2 family. Circles, females; squares, males; red in filled symbols indicate individuals with ANKRD26 (NM_014915) c.-128G > T mutation; yellow in filled symbols indicate individuals with HBB (NM_000518.5) c.52A > T mutation; green in filled symbols indicate individuals with HID1 (NM_030630) c.442G > T mutation. The proband is indicated by an arrowhead; symbol with a diagonal line indicates a deceased individual. (D) The platelet (PLT), mean platelet volume (MPV), white blood cell (WBC), hemoglobin (HGB), and thrombopoietin (TPO) levels were compared between THC2 and non-THC2 family members. The WHO bleeding score was compared between TBH (THC2 subjects who carry both beta-thalassemia and hypofibrinogenaemia mutations), non-TBH THC2 (THC2 subjects who do not carry both beta-thalassemia and hypofibrinogenaemia mutations) and non-THC2 (who do not have THC2) family members. (E) Mutation c.52A > T in HBB was confirmed by Sanger sequencing. (F) Mutation c.442G > T in HID1 was confirmed by Sanger sequencing. Unpaired Student's t-test was used to analyze the differences between 2 groups, one way ANOVA was used to analyze the differences between multiple groups.
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F2
SNP 6.0 under a completely penetrant autosomal-dominant model with a disease allele frequency of 0.0003. Sixteen family members (I1, I2, I3, II1, II2, II3, II4, II5, II6, II7, II8, III2, III3, III4, III5, and III6) were genotyped and the results showed the exceeded genome-wide significance for linkage at 10p12.31-p11.23 with a LOD score of 2.8 (Figure 2A). THC2, excepting for family members I6 and II13 (Table 1 and Figures 2B,C). No significant difference was observed for the HGB level between THC2 and non-THC2 family members (Table 1 and Figure 2D). We have also demonstrated that the pathogenic mutation of beta-thalassemia was c.52A > T (p.Lys18Ter) of HBB (NM_000518.5) (Figure 2E) which is very common in the Chinese population. HID1 (NM_030630) (Figure 2F) since some SNPs of HID1 was reported to be associated with decreased fibrinogen in a GWAS study. However, eight family members with HID1 c.442G > T mutation show a normal fibrinogen level.