Background
Methods
Patients
SNPs
Statistical analysis
Mutation detection
Transfection studies
3D-modeling
Results
Clinical form | One mutation | Two mutations | Total |
---|---|---|---|
Perinatal | 5 (6.4%) | 73 (93.6%) | 78 |
Infantile | 2 (3.3%) | 58 (96.7%) | 60 |
Childhood | 8 (23.5%) | 26 (76.4%) | 34 |
Adult | 12 (40.0%) | 18 (60.0%) | 30 |
Odontohypophosphatasia | 29 (74.3%) | 10 (25.6%) | 39 |
Total
|
56
|
185
|
241
|
Mutation | Activity (% WT) | Frequency |
---|---|---|
c.571G>A (p.E191K)/other | 56–88a
| 0.547 |
c.526G>A (p.A176T)/other | 30.2–45.4a
| 0.094 |
c.407G>A (p.R136H)/other | 33.4 | 0.075 |
c.1363G>A (p.G455S)/other | 71.0 | 0.038 |
c.815G>A (p.R272H)/other | 6.8 | 0.038 |
c.395C>T (p.A132V)/other | 16.9 | 0.019 |
other/other | 0.189 | |
Total
|
1.000
|
Patient | Mutation | Residual activity (%WT) | Dominant negative effect (%WT) | Parent carrier | Clinical symptoms in the parent carrier | Haplotypes | Trans or cis | Clin. form |
---|---|---|---|---|---|---|---|---|
1
| p.G456W | 0.8 | 14.5 | F | no | A/A | - | Ch |
2
| p.G420A | 4.2 | 19.7 | ? | no | A/C | - | Od |
3
| p.D378V | 1.2 | 19.9 | F | no | A/E | Cis likely | Ch |
4
| p.L414M | 0.4 | 23.5 | M | ? | A/C | - | Od |
5
| p.P108L | 1.9 | 24.0 | M | yes | A/E | trans | Od |
6
| p.N417S | 3.0 | 26.5 | M | no | A/A | - | Od |
7
| p.N417S | 3.0 | 26.5 | F | yes | A/E | trans | Od |
8
| p.N417S | 3.0 | 26.5 | ? | no | A/A | - | Ad |
9
| p.N417S | 3.0 | 26.5 | F | yes | A/A | - | Od |
10
| p.E452K | 1.4 | 27.5 | M | yes | A/B | - | Ad |
11
| p.T100M | 1.3 | 28.2 | M | no | A/E | Cis | Ch |
12
| p.R391H | 0 | 29.1 | ? | ? | B/E | Cis | Od |
13
| p.V382I | 0a
| 30a
| F | yes | A/J | - | Pb |
14
| p.R71H | 1.0 | 30.5 | ? | no | A/B | - | Od |
15
| p.R71H | 1.0 | 30.5 | M | ? | A/B | - | Od |
16
| p.R71H | 1.0 | 30.5 | M | no | A/C | - | Od |
17
| p.R71H | 1.0 | 30.5 | M | yes | E/E | Cis/trans | Od |
18
| p.E429K | 1.3 | 31.0 | F | no | B/E | Trans | Od |
19
| p.G339R | 1.1 | 33.0 | F | no | A/B | - | Od |
20
| p.G339R | 1.1 | 33.0 | F | yes | A/B | Od | |
21
| p.G339R | 1.1 | 33.0 | M | yes | B/E | Trans | Od |
22
| p.R71C | 2.5 | 35.0 | F | no | A/A | - | Od |
23
| p.R71C | 2.5 | 35.0 | M | no | A/C | - | Od |
24
| p.S445P | 2.1 | 35.1 | ? | ? | A/C | - | Ad |
25
| p.R184W | 0.6 | 36.7 | ? | ? | A/A | - | Ad |
26
| p.R184W | 0.6 | 36.7 | M | no | A/A | - | Od |
27
| p.R184W | 0.6 | 36.7 | F | yes | A/B | - | Ch |
28
| p.R184W | 0.6 | 36.7 | M | no | A/E | Trans | Od |
29
| p.N478I | 1.5 | 38.2 | ? | no | A/B | - | Ch |
30
| p.G334R | 5.0 | 39.0 | ? | no | A/C | - | Od |
31
| p.E476A | 0.4 | 39.3 | M | ? | A/E | Trans | Ad |
32
| p.G334D | 1.7 | 40.0 | P | no | A/E | Cis | Od |
33
| p.A116T | 0.6 | 40.0 | M | yes | A/E | Trans | Od |
34
| p.I72T | 5.1 | 40.2 | M | no | A/B | - | Od |
35
| p.V459L | 0 | 41.1 | ? | yes | A/A | - | Od |
36
| p.G122S | 4.5 | 43.6 | F | ? | A/A | - | Od |
37
| p.A111T | 2.0 | 48.7 | F | yes | E/E | Cis/trans | Od |
38
| p.R391C | 3.75 | 50.5 | M | ? | B/E | Trans | Ch |
39
| p.G456R | 1.5 | 50.5 | ? | no | A/D | - | Ad |
40
| p.G456R | 1.5 | 50.5 | ? | yes | A/A | - | Od |
41
| p.G456R | 1.5 | 50.5 | F | ? | A/E | Cis | Ch |
42
| p.A443V | 1.38 | 53.1 | ? | no | A/A | - | Ad |
43
| p.A176T | 30.2 | 58.0 | ? | ? | A/A | - | Ad |
44
| p.R136H | 33.4 | 70.0 | ? | ? | A/E | - | Ad |
45
| p.G249V | 34.5 | 70.5 | F | yes | A/C | - | Ch |
46
| p.I490F | 37.1 | 77.4 | ? | no | A/E | - | Ad |
47
| p.E191K | 56.0 | 79.5 | M | no | A/A | - | Od |
Haplotype | Patients with 1 mutation (n = 48) | Other patients (n = 74) | P value | ||
---|---|---|---|---|---|
Haplotype A: T-C-G-G-C-C-T-A | 54 (0.57) | 73 (0.79) | 99 (0.67) | 137 (0.93) | 1.9 10-1
|
Haplotype B: T-T-G-G-C-C-T-A | 12 (0.13) | 23 (0.16) | 6.2 10-1
| ||
Haplotype C: T-C-G-G-T-C-T-A | 7 (0.07) | 5 (0.03) | 1.4 10-1
| ||
Haplotype D: T-C-T-A-T-C-T-A | 1 (0.01) | 0 | |||
Haplotype F: T-C-T-A-T-C-T-A | 0 | 2 (0.02) | |||
Haplotype G: T-C-G-G-C-G-T-G | 0 | 2 (0.01) | |||
Haplotype H: C-C-T-A-T-G-T-G | 0 | 1 (0.01) | |||
Haplotype I: C-T-G-G-C-G-C-G | 0 | 1 (0.01) | |||
Haplotype J: C-T-G-G-T-C-T-A | 1 | 1 (0.01) | |||
Haplotype K: C-C-T-A-C-G-C-G | 0 | 2 (0.02) | |||
Haplotype L: T-T-G-G-T-C-T-A | 0 | 2 (0.02) | |||
Haplotype E: C-C-T-A-T-G-C-G | 19 (0.20) | 19 (0.21) | 10 (0.07) | 10 (0.07) | 1.4 10-3
|
Total
|
94
|
94
|
148
|
148
|