| Year . | Domain . | (non) coding region . | Mutation . | Ligand affinity . | Transactivating capacity . | Other in vitro observations . | Clinical features . | References . |
|---|---|---|---|---|---|---|---|---|
1982 | LB | Exon 7 | Asp641Val | ↓ (3-fold) | ↓↓ | Transrespressional capacity = Delayed nuclear translocation Abnormal interaction with the GR-interacting protein 1 coactivator mRNA GR copy number after EBV transformation ↓ | Hypertension, hypokalaemia | (2, 3, 4, 5) |
1990 | LB | Exon 9α | Val729Ile | ↓ | ↓ (4-fold) | Delayed nuclear translocation Abnormal interaction with the GR-interacting protein 1 coactivator | Isosexual precocious pseudopuberty in a boy, hyperandrogenism | (3, 6, 7) |
1993 | LB | Exon 6/ intron 6 | 4-base deletion (2013delGAGT) | Not tested | ↓ | Removal of a donor splice site, expression of only one allele and a 50% decrease of GR protein on PBMLs and EBV transformed lymphoblasts | Hirsutism, menstrual irregularities, male-pattern baldness | (4, 8) |
1996 | DB | Exon 5 | Ile559Asn | = binding sites by 50% ↓ | Dominant-negative effect on transactivation of the wild-type GR | Transrespressional capacity↓ mRNA GR copy number after EBV transformation ↓ Delayed nuclear translocation Abnormal interaction with the GR-interacting protein 1 coactivator | Hypertension, infertility, oligospermia, and secondary pituitary Cushing’s disease | (3, 4, 9,10) |
2001 | DB | Exon 4 | Arg477His | = | ↓↓ | In a structural model the mutant GR seems to have no contact with the GRE of the target gene | Hypertension, hirsutism, fatigue, obesity | (11, 12) |
2001 | LB | Exon 8 | Gly679Ser | ↓(2-fold) | ↓ | In heterozygous carriers the effect of the mutation was abolished when also the ER22/23EK polymorphism was present | Asymptomatic, hypertension, hypokalaemia hirsutism, fatigue, hyperandrogenism A dosage–allele effect was observed | (11, 12, 13) |
2002 | DB | Exon 5 | Val571Ala | ↓ (6-fold) | ↓ (10- to 50-fold) | Delayed nuclear translocation | Hypertension, hypokalaemia, hyperandrogenism, female pseudohermaphroditism | (3, 14) |
2002 | LB | Exon 9α | Ile747Met | ↓ (2-fold) | ↓↓ (20- to 30-fold) Dominant negative effect on the wild-type GR | Abnormal interaction with p160 coactivators due to an ineffective AF-2 domain | Asymptomatic, cystic acne, hirsutism, oligoamenorrhoea | (3, 15) |
2005 | LB | Exon 9α | Leu773Pro | ↓ (2.6-fold) | ↓(2-fold) | Delayed nuclear translocation Abnormal interaction with the GR-interacting protein 1 coactivator Dominant negative effect on the wild-type GR | Hypertension, chronic fatigue, anxiety, hyperandrogenism, | (16) |
2006 | LB | Intron 8 | G→A, +81 bp exon 8 and C→G -9 bp exon 9 | Not tested | ↓ | Transrespressional capacity = Expression of the GR-β splice variant ↑ (4-fold) | Despite low dose immunosuppressive medication 33 years after post mortem renal transplantation still uneventful | (4) |
2007 | LB | Exon 9α | Phe737Leu | ↓ (1.5-fold) | ↓ | Delayed nuclear translocation | Hypertension, hypokalaemia | (17) |
| Year . | Domain . | (non) coding region . | Mutation . | Ligand affinity . | Transactivating capacity . | Other in vitro observations . | Clinical features . | References . |
|---|---|---|---|---|---|---|---|---|
1982 | LB | Exon 7 | Asp641Val | ↓ (3-fold) | ↓↓ | Transrespressional capacity = Delayed nuclear translocation Abnormal interaction with the GR-interacting protein 1 coactivator mRNA GR copy number after EBV transformation ↓ | Hypertension, hypokalaemia | (2, 3, 4, 5) |
1990 | LB | Exon 9α | Val729Ile | ↓ | ↓ (4-fold) | Delayed nuclear translocation Abnormal interaction with the GR-interacting protein 1 coactivator | Isosexual precocious pseudopuberty in a boy, hyperandrogenism | (3, 6, 7) |
1993 | LB | Exon 6/ intron 6 | 4-base deletion (2013delGAGT) | Not tested | ↓ | Removal of a donor splice site, expression of only one allele and a 50% decrease of GR protein on PBMLs and EBV transformed lymphoblasts | Hirsutism, menstrual irregularities, male-pattern baldness | (4, 8) |
1996 | DB | Exon 5 | Ile559Asn | = binding sites by 50% ↓ | Dominant-negative effect on transactivation of the wild-type GR | Transrespressional capacity↓ mRNA GR copy number after EBV transformation ↓ Delayed nuclear translocation Abnormal interaction with the GR-interacting protein 1 coactivator | Hypertension, infertility, oligospermia, and secondary pituitary Cushing’s disease | (3, 4, 9,10) |
2001 | DB | Exon 4 | Arg477His | = | ↓↓ | In a structural model the mutant GR seems to have no contact with the GRE of the target gene | Hypertension, hirsutism, fatigue, obesity | (11, 12) |
2001 | LB | Exon 8 | Gly679Ser | ↓(2-fold) | ↓ | In heterozygous carriers the effect of the mutation was abolished when also the ER22/23EK polymorphism was present | Asymptomatic, hypertension, hypokalaemia hirsutism, fatigue, hyperandrogenism A dosage–allele effect was observed | (11, 12, 13) |
2002 | DB | Exon 5 | Val571Ala | ↓ (6-fold) | ↓ (10- to 50-fold) | Delayed nuclear translocation | Hypertension, hypokalaemia, hyperandrogenism, female pseudohermaphroditism | (3, 14) |
2002 | LB | Exon 9α | Ile747Met | ↓ (2-fold) | ↓↓ (20- to 30-fold) Dominant negative effect on the wild-type GR | Abnormal interaction with p160 coactivators due to an ineffective AF-2 domain | Asymptomatic, cystic acne, hirsutism, oligoamenorrhoea | (3, 15) |
2005 | LB | Exon 9α | Leu773Pro | ↓ (2.6-fold) | ↓(2-fold) | Delayed nuclear translocation Abnormal interaction with the GR-interacting protein 1 coactivator Dominant negative effect on the wild-type GR | Hypertension, chronic fatigue, anxiety, hyperandrogenism, | (16) |
2006 | LB | Intron 8 | G→A, +81 bp exon 8 and C→G -9 bp exon 9 | Not tested | ↓ | Transrespressional capacity = Expression of the GR-β splice variant ↑ (4-fold) | Despite low dose immunosuppressive medication 33 years after post mortem renal transplantation still uneventful | (4) |
2007 | LB | Exon 9α | Phe737Leu | ↓ (1.5-fold) | ↓ | Delayed nuclear translocation | Hypertension, hypokalaemia | (17) |
↓, reduced; ↓↓, severely reduced; =, unaltered.
DB, DNA binding domain; EBV, Epstein–Barr virus; GR, glucocorticoid receptor; GRE, glucocorticoid responsive element; LB, ligand-binding domain; PBML, peripheral blood mononuclear leucocytes.
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