Features of families with ACTN1 mutations
| Family (number of individuals) . | Mean age at diagnosis, years (range) . | World Health Organization bleeding score* . | Mean platelet count,†,‡ ×109/L (range) . | Mean platelet volume,† fL (range) . | Mean platelet diameter,¶ μm (range) . | ACTN1 mutation . |
|---|---|---|---|---|---|---|
| F1 (4) | 43 (22-55) | 0 (1), 1 (3) | 107 (89-134) | 11.1 (10.1-12.0) | 2.8 (2.7-3.0) | p.Asp22Asn |
| F2 (4) | 46 (26-64) | 0 (1), 1 (2), 2 (1) | 103 (81-118) | 12.5 (10.6-14.7) | 3.3 (3.0-3.7) | p.Arg46Trp |
| F3 (4) | 42 (14-72) | 0 (1), 1 (1), 2 (2) | 95 (66-124) | 14.8 (14.0-15.6) | 3.8 (3.5-4.1) | p.Arg46Trp |
| F4 (2) | 30 (12-49) | 0 (2) | 103 (97-110) | 11.8 [11.3-12.4) | 3 (2.8-3.1) | p.Glu225Lys |
| F5 (6) | 23 (7-44) | 0 (1), 1 (3), 2 (3) | 103 (78-154) | 12.3 [10.4-14.0) | 3.3 (2.6-4.3] | p.Gly251Arg |
| F6 (2) | 58 (34-82) | 2 (2) | 58 (55-62) | 10.5 [10.4-10.6) | 3.2 (2.9-3.5] | p.Thr737Asn |
| F7 (1) | nd | 0 (1) | 110 | 12.1 | 2.5 | p.Arg738Trp |
| F8 (3) | 25 [3-44) | 0 (2), 1 (1) | 112 (65-166) | 12.5 (11.3-14.3) | 2.8 (2.6-3.0] | p.Arg752Gln |
| F9 (1) | 48 | 0 (1) | 117 | 14.4 | 3.3 | p.Gly764Ser |
| F10 (4) | 38 [3-66) | 0 (1), 1 (2), 2 (1) | 86 (46-120) | 14-3 [12.6-15) | 3.5 (2.9-3.9) | p.Glu769Lys |
| Family (number of individuals) . | Mean age at diagnosis, years (range) . | World Health Organization bleeding score* . | Mean platelet count,†,‡ ×109/L (range) . | Mean platelet volume,† fL (range) . | Mean platelet diameter,¶ μm (range) . | ACTN1 mutation . |
|---|---|---|---|---|---|---|
| F1 (4) | 43 (22-55) | 0 (1), 1 (3) | 107 (89-134) | 11.1 (10.1-12.0) | 2.8 (2.7-3.0) | p.Asp22Asn |
| F2 (4) | 46 (26-64) | 0 (1), 1 (2), 2 (1) | 103 (81-118) | 12.5 (10.6-14.7) | 3.3 (3.0-3.7) | p.Arg46Trp |
| F3 (4) | 42 (14-72) | 0 (1), 1 (1), 2 (2) | 95 (66-124) | 14.8 (14.0-15.6) | 3.8 (3.5-4.1) | p.Arg46Trp |
| F4 (2) | 30 (12-49) | 0 (2) | 103 (97-110) | 11.8 [11.3-12.4) | 3 (2.8-3.1) | p.Glu225Lys |
| F5 (6) | 23 (7-44) | 0 (1), 1 (3), 2 (3) | 103 (78-154) | 12.3 [10.4-14.0) | 3.3 (2.6-4.3] | p.Gly251Arg |
| F6 (2) | 58 (34-82) | 2 (2) | 58 (55-62) | 10.5 [10.4-10.6) | 3.2 (2.9-3.5] | p.Thr737Asn |
| F7 (1) | nd | 0 (1) | 110 | 12.1 | 2.5 | p.Arg738Trp |
| F8 (3) | 25 [3-44) | 0 (2), 1 (1) | 112 (65-166) | 12.5 (11.3-14.3) | 2.8 (2.6-3.0] | p.Arg752Gln |
| F9 (1) | 48 | 0 (1) | 117 | 14.4 | 3.3 | p.Gly764Ser |
| F10 (4) | 38 [3-66) | 0 (1), 1 (2), 2 (1) | 86 (46-120) | 14-3 [12.6-15) | 3.5 (2.9-3.9) | p.Glu769Lys |
nd, not determined.
World Health Organization bleeding score: grade 0, no bleeding; grade 1, only cutaneous bleeding; grade 2, mild blood loss; grade 3, gross blood loss, requiring transfusion; grade 4, debilitating blood loss, retinal or cerebral, associated with fatality.
Platelet count and mean platelet volume were measured with a Cell-Dyn Sapphire hematology analyzer (Abbott) in EDTA-anticoagulated blood samples within 1 hour from venipuncture.
One individual from family 5 and 1 person from family 8 with more than 150 × 109 platelets/L (bold) were classified as thrombocytopenic according to the recently proposed age- and sex-specific reference intervals.9
Mean platelet diameter was measured on peripheral blood films by optical microscopy and software-assisted image analysis (Axio-vision 4.5; Carl Zeiss), as previously reported.10 In brief, blood smears prepared with non-anticoagulated blood from fingerstick were stained with May-Grünwald-Giemsa staining, and the mean platelet diameter was calculated from 200 different cells.