TABLE 2.
Mutations of the Human Glucocorticoid Receptor Gene Causing Generalized Glucocorticoid Resistance
| Mutation Position |
|||
|---|---|---|---|
| Author (Reference) | cDNA | Amino acid | Molecular Mechanisms |
| Chrousos et al. (64) | 1922 (A→T) | 641 (D→V) | Transactivation ↓ |
| Hurley et al. (71) | Affinity for ligand ↓ (x 3) | ||
| Nuclear translocation: 22 min | |||
| Abnormal interaction with GRIP1 | |||
| Karl et al. (72) | 4 bp deletion in exon-intron 6 | hGRαnumber: 50% of control | |
| Inactivation of the affected allele | |||
| Malchoff et al. (73) | 2185 (G→A) | 729 (V→I) | Transactivation ↓ |
| Affinity for ligand ↓ (x 2) | |||
| Nuclear translocation: 120 min | |||
| Abnormal interaction with GRIP1 | |||
| Karl et al. (70) | 1676 (T→A) | 559 (I→N) | Transactivation ↓ |
| Decrease in hGR binding sites | |||
| Transdominance (+) | |||
| Nuclear translocation: 180 | |||
| Abnormal interaction with GRIP1 | |||
| Ruiz et al. (75) | 1430 (G→A) | 477 (R→H) | Transactivation ↓ |
| Charmandari et al. (80) | No DNA binding | ||
| Nuclear translocation: 20 min | |||
| Ruiz et al. (75) | 2035 (G→A) | 679 (G→S) | Transactivation ↓ |
| Charmandari et al. (80) | Affinity for ligand ↓(x 2) | ||
| Nuclear translocation: 30 min | |||
| Abnormal interaction with GRIP1 | |||
| Mendonca et al. (76) | 1712 (T→C) | 571 (V→A) | Transactivation ↓ |
| Affinity for ligand ↓ (x 6) | |||
| Nuclear translocation: 25 min | |||
| Abnormal interaction with GRIP1 | |||
| Vottero et al. (77) | 2241 (T→G) | 747 (I→M) | Transactivation ↓ |
| Transdominance (+) | |||
| Affinity for ligand ↓ (x 2) | |||
| Nuclear translocation ↓ | |||
| Abnormal interaction with GRIP1 | |||
| Charmandari et al. (79) | 2318 (T→C) | 773 (L→P) | Transactivation ↓ |
| Transdominance (+) | |||
| Affinity for ligand ↓ (x 2.6) | |||
| Nuclear translocation: 30 min | |||
| Abnormal interaction with GRIP1 | |||
| Charmandari et al. (81) | 2209 (T→C) | 737 (F→L) | Transactivation ↓ |
| Transdominance/time-dependent (+) | |||
| Affinity for ligand ↓ (x 1.5) | |||
| Nuclear translocation: 180 min | |||
Adapted from Reference 78