中华医学杂志（英文版）2011，Vol.124Issue(4)：551-555,5.DOI:10.3760/cma.j.issn.0366-6999.2011.04.013
Generalized glucocorticoid resistance accompanied with an adrenocortical adenoma and caused by a novel point mutation of human glucocorticoid receptor gene
Generalized glucocorticoid resistance accompanied with an adrenocortical adenoma and caused by a novel point mutation of human glucocorticoid receptor gene
ZHU Hui-juan 1GONG Feng-ying 1DAI Yu-fei 1WANG Ou 1LI Mei 1LU Lin 1ZHAO Wei-gang 1XING Xiao-ping 1PAN Hui 2LI Nai-shi1
作者信息
- 1. Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
- 2. Department of Medical Education, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
- 折叠
摘要
Abstract
Background Generalized glucocorticoid resistance syndrome is a rare familial or sporadic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. This syndrome is partially caused by mutations in human glucocorticoid receptor (hGR) gene. The clinical spectrum of generalized glucocorticoid resistance is broad, ranging from fatigue or no symptoms to severe hypertension with hypokalemic alkalosis. The purpose of this study was to explore the genetic disorder of glucocorticoid resistance syndrome.Methods We identified a 56-year-old male patient diagnosed with generalized glucocorticoid resistance syndrome accompanied with an adrenocortical adenoma. This asymptomatic patient referred to Peking Union Medical College Hospital for treatment of his adrenal incidentaloma. Endocrinological evaluation consistently revealed his elevated serum cortisol level. Total RNA was extracted from the patient's peripheral blood mononuclear leukocytes (PBMLs) and entire coding region of hGR alpha was amplified by reverse transcription (RT)-PCR. To confirm the possible mutation identified by sequencing RT-PCR products, genomic DNA sequence of hGR gene from the patient and 50 healthy controls was analyzed by PCR and directly sequencing.Results A heterozygotic (C→T) substitution at nucleotide position of 1667 (exon 5) in GR alpha gene was found in this patient by sequencing of RT-PCR products of hGR gene. This substitution was also identified at genomic DNA level and it was absent in 100 chromosomes from 50 unrelated health controls. This substitution resulted in a threonine to isoleucine substitution (ACT→ATT) at amino acid 556 in the ligand-binding domain of GR alpha. Conclusion Generalized glucocorticoid resistance in this patient might be caused by a novel heterozygotic mutation in the ligand-binding domain of the GR alpha.关键词
generalized glucocorticoid resistance/adrenal adenoma/glucocorticoid receptor/gene mutationKey words
generalized glucocorticoid resistance/adrenal adenoma/glucocorticoid receptor/gene mutation引用本文复制引用
ZHU Hui-juan,GONG Feng-ying,DAI Yu-fei,WANG Ou,LI Mei,LU Lin,ZHAO Wei-gang,XING Xiao-ping,PAN Hui,LI Nai-shi..Generalized glucocorticoid resistance accompanied with an adrenocortical adenoma and caused by a novel point mutation of human glucocorticoid receptor gene[J].中华医学杂志（英文版）,2011,124(4):551-555,5.
