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A novel mutation in the glucocorticoid receptor gene as a cause of severe glucocorticoid resistance complicated by hypertensive encephalopathy

Tatsi, Christinaa; Xekouki, Paraskevia; Nioti, Olgaa; Bachrach, Bertb; Belyavskaya, Elenaa; Lyssikatos, Charalamposa; Stratakis, Constantine A.a

doi: 10.1097/HJH.0000000000002048
ORIGINAL PAPERS: Secondary hypertension

Background: Glucocorticoid resistance syndrome (GRS) is caused by mutations of the glucocorticoid receptor (coded by the NR3C1 gene) and presents with signs of mineralocorticoid and/or androgen excess.

Patient: A female patient presented at the age of almost 3 years with hypertensive and hypoglycemic seizure. She was diagnosed with GRS and was treated with antihypertensive medications and dexamethasone. She was later found to have MRI findings of punctuate microinfarcts at the basal ganglia, left thalamus and pons, possibly associated with uncontrolled hypertension. Increase of the dexamethasone dose up to 14 mg/day resulted in sufficient control of her symptoms.

Results: Two mutations in the NR3C1 gene were identified: a novel mutation in exon 2 (p.E198X), and a previously described mutation in exon 8 (p.R714Q).

Conclusion: GRS may present with life-threatening complications; this is the first report of hypertensive encephalopathy in association with GRS. Successful management of patients might require high doses of dexamethasone to control blood pressure.

aSection on Genetics and Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland

bPediatric Diabetes and Endocrinology Department, University of Missouri Children's Hospital, Columbia, Missouri, USA

Correspondence to Constantine A. Stratakis, MD, D(Med)Sc, SEGEN, PDEGEN, NICHD, NIH, 10 Center Drive, Building 10, NIH-Clinical Research Center, Room 1-3330, MSC1103, Bethesda, MD 20892, USA. Tel: +00 1 301 496 4686; fax: +00 1 301 4020574; e-mail:

Abbreviations: CNS, central nervous system; GRS, glucocorticoid resistance syndrome; HPE, holoprosencephaly; LBD, ligand binding domain; NMD, nonsense-mediated mRNA decay; PROVEAN, Protein Variation Effect Analyzer; SIFT, sorting intolerant from tolerant; WES, whole exome sequencing

Received 9 November, 2018

Revised 16 December, 2018

Accepted 18 December, 2018

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