Table 1.
Human disease-associated LMNA mutations used in this study
| Mutation | Disease | Reference |
|---|---|---|
| ΔK32 | EDMD | (68) |
| R60G | DCM-CD, DCM-CD + FPLD, DCM-CD + FPLD + CMT2 | (62) |
| L85R | DCM-CD | (62) |
| N195K | DCM-CD | (62) |
| E203G | DCM-CD | (62) |
| E203K | DCM-CD | (77) |
| E358K | EDMD | (78) |
| M371K | EDMD | (78) |
| R386K | EDMD | (78) |
| R453W | EDMD, EDMD + FPLD, LGMD1B | (78) |
| R482Q | FPLD | (79) |
| R482W | FPLD, FPLD + LGMD | (80) |
| K486N | FPLD | (81) |
| W520S | EDMD | (78) |
| R527P | EDMD, EDMD + FPLD, LGMD1B | (82) |
| T528K | EDMD, LGMD1B | (78) |
| L530P | EDMD | (82) |
| ΔNLA | Synthetic dominant-negative construct | (35) |
The tested mutations were R60G, L85R, N195K E203K and E203G, causing DCM (62,77); ΔK32, E358K, M371K, R386K, R453W, W520S, R527P, T528K and L530P, found in patients with EDMD (68,78,82); and R482Q, R482W and K486N, identified in patients with FPLD (79–81). In addition, we expressed the engineered dominant-negative construct ΔNLA, which disrupts endogenous lamin organization (35). Note that, although most mutations affect both lamin A and lamin C, we expressed only modified lamin A in MEF cells.
EDMD, Emery–Dreifuss muscular dystrophy; LGMD1B, limb–girdle muscular dystrophy type 1B; DCM-CD, dilated cardiomyopathy with conduction defect; CMT2, autosomal recessive Charcot–Marie–Tooth disease; FPLD, familial partial lipodystrophy type Dunnigan (FPLD2). For additional information on these mutations, see also http://www.umd.be/LMNA/.