Recent advances in the molecular mechanisms determining tissue sensitivity to glucocorticoids: novel mutations, circadian rhythm and ligand-induced repression of the human glucocorticoid receptor

Nicolaides, Nicolas C; Charmandari, Evangelia; Chrousos, George P; Kino, Tomoshige

doi:10.1186/1472-6823-14-71

Table 3 Mutations of the human glucocorticoid receptor gene causing primary generalized glucocorticoid resistance or hypersensitivity

From: Recent advances in the molecular mechanisms determining tissue sensitivity to glucocorticoids: novel mutations, circadian rhythm and ligand-induced repression of the human glucocorticoid receptor

Mutation position
Author (Reference)	cDNA	Amino acid	Molecular mechanisms	Genotype	Phenotype
Chrousos et al.[27]	1922 (A → T)	641 (D → V)	Transactivation ↓	Homozygous	Hypertension
Hurley et al.[32]			Affinity for ligand ↓ (× 3)		Hypokalemic alkalosis
			Nuclear translocation: 22 min
			Abnormal interaction with GRIP1
Karl et al. [33]	4 bp deletion in		hGRα number: 50% of control	Heterozygous	Hirsutism
	exon-intron 6		Inactivation of the affected allele		Male-pattern hair-loss
					Menstrual irregularities
Malchoff et al.[34]	2185 (G → A)	729 (V → I)	Transactivation ↓	Homozygous	Precocious puberty
			Affinity for ligand ↓ (× 2)		Hyperandrogenism
			Nuclear translocation: 120 min
			Abnormal interaction with GRIP1
Karl et al.[31]	1676 (T → A)	559 (I → N)	Transactivation ↓	Heterozygous	Hypertension
Kino et al.[35]			Decrease in hGR binding sites		Oligospermia
			Transdominance (+)		Infertility
			Nuclear translocation: 180 min
			Abnormal interaction with GRIP1
Ruiz et al.[36]	1430 (G → A)	477 (R → H)	Transactivation ↓	Heterozygous	Hirsutism
Charmandari et al.[41]			No DNA binding		Fatigue
			Nuclear translocation: 20 min		Hypertension
Ruiz et al.[36]	2035 (G → A)	679 (G → S)	Transactivation ↓	Heterozygous	Hirsutism
Charmandari et al.[41]			Affinity for ligand ↓ (× 2)		Fatigue
			Nuclear translocation: 30 min		Hypertension
			Abnormal interaction with GRIP1
Mendonca et al.[37]	1712 (T → C)	571 (V → A)	Transactivation ↓	Homozygous	Ambiguous genitalia
			Affinity for ligand ↓ (× 6)		Hypertension
			Nuclear translocation: 25 min		Hypokalemia
			Abnormal interaction with GRIP1		Hyperandrogenism
Vottero et al.[38]	2241 (T → G)	747 (I → M)	Transactivation ↓	Heterozygous	Cystic acne
			Transdominance (+)		Hirsutism
			Affinity for ligand ↓ (× 2)		Oligo-amenorrhea
			Nuclear translocation ↓
			Abnormal interaction with GRIP1
Charmandari et al.[40]	2318 (T → C)	773 (L → P)	Transactivation ↓	Heterozygous	Fatigue
			Transdominance (+)		Anxiety
			Affinity for ligand ↓ (× 2.6)		Acne
			Nuclear translocation: 30 min		Hirsutism
			Abnormal interaction with GRIP1		Hypertension
Charmandari et al.[42]	2209 (T → C)	737 (F → L)	Transactivation ↓	Heterozygous	Hypertension
			Transdominance (time-dependent) (+)		Hypokalemia
			Affinity for ligand ↓ (× 1.5)
			Nuclear translocation: 180 min
McMahon et al.[43]	2 bp deletion	773	Transactivation ↓	Homozygous	Hypoglycemia
	at nt 2318-9		Affinity for ligand: absent		Fatigability with feeding
			No suppression of IL-6		Hypertension
Nader et al.[44]	2141 (G → A)	714 (R → Q)	Transactivation ↓	Heterozygous	Hypoglycemia
			Transdominance (+)		Hypokalemia
			Affinity for ligand ↓ (× 2)		Hypertension
			Nuclear translocation ↓		Mild clitoromegaly
			Abnormal interaction with GRIP1		Advanced bone age
					Precocious pubarche
Zhu Hui-juan et al.[45]	1667 (G → T)	556 (T → I)	Not studied yet	Heterozygous	Adrenal incidentaloma
Charmandari et al.[46]	1201 (G → C)	401 (D → H)	Transactivation ↑	Heterozygous	Visceral obesity
			Transdominance (+)		Hypercholesterolemia
			Affinity for ligand: N		Hypertriglyceridemia
			Nuclear translocation: N		Hypertension
			Interaction with GRIP1: N		Diabetes type 2
Roberts et al.[47]	1268 (T → C)	423 (V → A)	Transactivation ↓	Heterozygous	Fatigue
			Affinity for ligand: N		Anxiety
			No DNA binding		Hypertension
			Nuclear translocation: 35 min
			Interaction with GRIP1: N
Nicolaides et al.[48]	1724 (T → G)	575 (V → G)	Transactivation ↓	Heterozygous	Melanoma
			Transrepression ↑		Asymptomatic daughters
			Affinity for ligand ↓ (× 2)
			Nuclear translocation ↓
			Abnormal interaction with GRIP1

Modified from References [29] and [30].
Numbers in the parentheses following authors’ names indicate the corresponding references.

Back to article page

ISSN: 1472-6823

Contact us

General enquiries: journalsubmissions@springernature.com

BMC Endocrine Disorders

Contact us