Table 1.
Correlation of the effects of KCNT1 mutations on the electrophysiological properties of KCNT1 currents with patient phenotypes. KCNT1 current amplitude is expressed as fold increase, compared to the amplitude of the WT KCNT1 current (derived from the data on Figure 2). Apparent Po at −80 mV is taken from the data shown in Figure 4. The kinetics of KCNT1 current is expressed as a time constant of an exponential function fitted to KCNT1 current traces obtained in response to 600 ms voltage steps to 80 mV.
|
KCNT1 Mutation/ Location |
Patient Phenotype (Severity Score) |
K+ Current Amplitude (Fold Increase) |
Apparent Po at −80 mV (%) (n = 4–9) |
Kinetics τ (ms) (n = 4–8) |
|---|---|---|---|---|
| G288S /S5 |
Severe (EIMFS), less severe (2) (SHE) or unaffected |
21 | 20 ± 2.8 | 197 ± 16 |
| T314A /P-loop |
Severe (atypical DEE with (3) severe ID) | 1.2 | 82 ± 5.7 | N/A |
| R398Q /RCK1 |
Severe (EIMFS or DEE), less (2) severe (SHE) or unaffected | 13 | 25 ± 4.6 | 161 ± 11 |
| N449S /RCK1 |
Less severe (1) (SHE with mild ID) |
4 | 18 ± 3.5 | 175 ± 12 |
| L781V /adj RCK2 |
Severe (3) (DEE and severe ID) |
42 | 73 ± 2.6 | 33 ± 5 |
| E893K /NAD+ |
Severe (3) (EIMFS) |
13 | 76 ± 7.7 | 42 ± 5 |
| M896V /NAD+ |
Severe (EIMFS or DEE) (2) or less severe (SHE) |
36 | 54 ± 8.0 | 51 ± 4 |
| R928C /RCK2 |
Less severe (1) (SHE or TLE) |
21 | 67 ± 6.8 | 16 ± 3 |
| F932L /RCK2 |
Moderate (2) (SHE with moderate ID) |
14 | 52 ± 3.1 | 52 ± 3 |
| S937G /RCK2 |
Moderate (2) (DEE or SHE) |
14 | 33 ± 5.6 | 113 ± 6 |
| L942F /RCK2 |
Less severe (1) (SHE) |
10 | 39 ± 3.8 | 226 ± 9 |
| R961H /RCK2 |
Moderate (SHE with (2) cognitive regression) |
8 | 23 ± 4.7 | 88 ± 6 |
| A965T /RCK2 |
Less severe (1) (SHE) |
14 | 35 ± 6.3 | 139 ± 7 |
Abbreviations in the table: EIMFS—Epilepsy of Infancy with Migrating Focal Seizures; SHE—Sleep-Related Hypermotor Epilepsy; DEE—Developmental and Epileptic Encephalopathies; TLE—Temporal Lobe Epilepsy; ID—Intellectual Disability.