Mutations and phenotypic VWF parameters of 57 patients with VWD 2A/IIE
| Exon . | nt . | aa . | Ag 0.5 . | SD . | CB 0.8 . | SD . | Ratio CB . | RCo 0.5 . | SD . | Ratio RCo . | FVIII 0.6 . | SD . | bt < 6′ . | s . | bs* . | IC† . | C‡ . | ref . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 22 | 2867T>C | V956A | 0.31 | 0.37 | 1.19 | 0.25 | 0.81 | 0.62 | — | m | (1) | 1 | 1 | novel | ||||
| 22 | 2926C>T | R976C | 1.29 | 0.46 | 1.04 | 0.25 | 0.81 | — | ND | 0.85 | 0.09 | — | m | (2) | 3 | 5 | novel | |
| 25 | 3271T>C | C1091R | 1.20 | 1.20 | 1.00 | — | ND | — | — | m | (3) | 1 | 1 | novel | ||||
| 25 | 3314C>A | A1105D | 0.14 | 0.13 | 0.93 | 0.11 | 0.79 | — | — | — | — | 1 | 1 | novel | ||||
| 25 | 3359G>C | W1120S | 0.34 | 0.19 | 0.56 | 0.21 | 0.62 | 0.72 | 20 | — | — | 1 | 2 | 28 | ||||
| 25 | 3362G>T | R1121M | 0.23 | 0.20 | 0.87 | — | — | — | — | — | — | 1 | 1 | novel | ||||
| 25 | 3377G>T | C1126F | 0.18 | 0.02 | 0.07 | 0.01 | 0.36 | — | — | — | — | — | — | 1 | 3 | novel | ||
| 26 | 3388T>C | C1130R | 0.17 | 0.10 | 0.59 | — | — | — | — | — | — | 1 | 1 | 29 | ||||
| 26 | 3387C>G | C1130W | 0.22 | 0.08 | 0.36 | — | — | — | — | — | — | 1 | 1 | novel | ||||
| 26 | 3437A>C | Y1146C | 0.20 | 0.07 | 0.16 | 0.06 | 0.79 | 0.07 | 0.03 | 0.35 | 0.31 | 0.08 | 11 | m-s | (4) | 12 | 17 | 29 |
| 26 | 3446G>A | C1149Y | 0.17 | 0.01 | 0.05 | 0.03 | 0.30 | 0.07 | 0.42 | 0.25 | — | m-s | (5) | 1 | 6 | novel | ||
| 26 | 3458G>A | C1153Y | 0.89 | 0.27 | 0.55 | 0.21 | 0.62 | 0.40 | 0.45 | 0.56 | — | — | — | 2 | 2 | novel | ||
| 26 | 3507T>G | C1169W | 0.11 | 0.05 | — | — | 0.06 | 0.01 | 0.52 | 0.17 | 0.05 | — | — | — | 1 | 2 | novel | |
| 26 | 3514G>T | G1172C | 0.25 | 0.14 | 0.56 | 0.15 | 0.60 | 0.45 | — | m | (6) | 1 | 1 | novel | ||||
| 26 | 3517T>C | C1173R | 0.19 | 0.08 | 0.42 | 0.10 | 0.53 | 0.61 | 12 | — | — | 1 | 1 | novel | ||||
| 26 | 3518G>T | C1173F | 0.35 | 0.11 | 0.23 | 0.04 | 0.65 | 0.32 | 0.93 | 0.54 | — | — | — | 3 | 4 | novel | ||
| 27 | 3568T>C | C1190R | 0.41 | 0.24 | 0.59 | 0.14 | 0.34 | 0.56 | 8 | — | — | 1 | 1 | 30 | ||||
| 27 | 3569G>A | C1190Y | 0.94 | 0.18 | 0.19 | — | — | — | — | — | — | 1 | 1 | novel | ||||
| 27 | 3583G>T | D1195Y | 0.43 | 0.38 | 0.88 | — | — | — | — | — | — | 1 | 1 | novel | ||||
| 28 | 3679T>C | C1227R | 0.03 | 0.01 | 0.33 | — | — | — | — | — | — | 1 | 1 | 31 | ||||
| 28 | 3833T>C | L1278P | 0.59 | 0.30 | 0.31 | 0.10 | 0.52 | — | — | — | — | — | — | 1 | 3 | novel | ||
| 28 | 3833T>G | L1278R | 0.20 | 0.21 | 1.05 | 0.02 | 0.10 | 0.26 | 20 | — | — | 1 | 1 | novel |
| Exon . | nt . | aa . | Ag 0.5 . | SD . | CB 0.8 . | SD . | Ratio CB . | RCo 0.5 . | SD . | Ratio RCo . | FVIII 0.6 . | SD . | bt < 6′ . | s . | bs* . | IC† . | C‡ . | ref . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 22 | 2867T>C | V956A | 0.31 | 0.37 | 1.19 | 0.25 | 0.81 | 0.62 | — | m | (1) | 1 | 1 | novel | ||||
| 22 | 2926C>T | R976C | 1.29 | 0.46 | 1.04 | 0.25 | 0.81 | — | ND | 0.85 | 0.09 | — | m | (2) | 3 | 5 | novel | |
| 25 | 3271T>C | C1091R | 1.20 | 1.20 | 1.00 | — | ND | — | — | m | (3) | 1 | 1 | novel | ||||
| 25 | 3314C>A | A1105D | 0.14 | 0.13 | 0.93 | 0.11 | 0.79 | — | — | — | — | 1 | 1 | novel | ||||
| 25 | 3359G>C | W1120S | 0.34 | 0.19 | 0.56 | 0.21 | 0.62 | 0.72 | 20 | — | — | 1 | 2 | 28 | ||||
| 25 | 3362G>T | R1121M | 0.23 | 0.20 | 0.87 | — | — | — | — | — | — | 1 | 1 | novel | ||||
| 25 | 3377G>T | C1126F | 0.18 | 0.02 | 0.07 | 0.01 | 0.36 | — | — | — | — | — | — | 1 | 3 | novel | ||
| 26 | 3388T>C | C1130R | 0.17 | 0.10 | 0.59 | — | — | — | — | — | — | 1 | 1 | 29 | ||||
| 26 | 3387C>G | C1130W | 0.22 | 0.08 | 0.36 | — | — | — | — | — | — | 1 | 1 | novel | ||||
| 26 | 3437A>C | Y1146C | 0.20 | 0.07 | 0.16 | 0.06 | 0.79 | 0.07 | 0.03 | 0.35 | 0.31 | 0.08 | 11 | m-s | (4) | 12 | 17 | 29 |
| 26 | 3446G>A | C1149Y | 0.17 | 0.01 | 0.05 | 0.03 | 0.30 | 0.07 | 0.42 | 0.25 | — | m-s | (5) | 1 | 6 | novel | ||
| 26 | 3458G>A | C1153Y | 0.89 | 0.27 | 0.55 | 0.21 | 0.62 | 0.40 | 0.45 | 0.56 | — | — | — | 2 | 2 | novel | ||
| 26 | 3507T>G | C1169W | 0.11 | 0.05 | — | — | 0.06 | 0.01 | 0.52 | 0.17 | 0.05 | — | — | — | 1 | 2 | novel | |
| 26 | 3514G>T | G1172C | 0.25 | 0.14 | 0.56 | 0.15 | 0.60 | 0.45 | — | m | (6) | 1 | 1 | novel | ||||
| 26 | 3517T>C | C1173R | 0.19 | 0.08 | 0.42 | 0.10 | 0.53 | 0.61 | 12 | — | — | 1 | 1 | novel | ||||
| 26 | 3518G>T | C1173F | 0.35 | 0.11 | 0.23 | 0.04 | 0.65 | 0.32 | 0.93 | 0.54 | — | — | — | 3 | 4 | novel | ||
| 27 | 3568T>C | C1190R | 0.41 | 0.24 | 0.59 | 0.14 | 0.34 | 0.56 | 8 | — | — | 1 | 1 | 30 | ||||
| 27 | 3569G>A | C1190Y | 0.94 | 0.18 | 0.19 | — | — | — | — | — | — | 1 | 1 | novel | ||||
| 27 | 3583G>T | D1195Y | 0.43 | 0.38 | 0.88 | — | — | — | — | — | — | 1 | 1 | novel | ||||
| 28 | 3679T>C | C1227R | 0.03 | 0.01 | 0.33 | — | — | — | — | — | — | 1 | 1 | 31 | ||||
| 28 | 3833T>C | L1278P | 0.59 | 0.30 | 0.31 | 0.10 | 0.52 | — | — | — | — | — | — | 1 | 3 | novel | ||
| 28 | 3833T>G | L1278R | 0.20 | 0.21 | 1.05 | 0.02 | 0.10 | 0.26 | 20 | — | — | 1 | 1 | novel |
Phenotypic parameters are given in U/mL with lower range limit: Ag indicates VWF:Ag; CB, VWF:collagen binding; RCo, VWF:Ristocetin Cofactor; FVIII, FVIII:C; SD, standard deviation. Mean values and SDs are given for mutations that were identified in more than 1 patient. Ratio indicates ratios of VWF functional parameters to VWF:Ag; bt, bleeding time; s, severity of the bleeding phenotype; bs, reported bleeding symptoms; nt, nucleotide change; aa, predicted amino acid change; IC, number of index cases; C, number of cases; —, no data; ref, literature reference; and ND, not done.
Reported bleeding symptoms: (1) menorrhagia; (2) epistaxis; (3) epistaxis, oral mucosal bleeding, hematoma; (4) epistaxis, hematoma, menorrhagia, hematuria, intestinal bleeding, joint bleeding requiring prophylaxis; (5) epistaxis, hematoma, menorrhagia, hematuria, bleeding after adenectomy, intestinal bleeding, joint bleeding, CNS bleeding; and (6) epistaxis, oral mucosal bleeding.
Total number of ICs was 38.
Total number of cases was 57.