Five missense variants in the amino-terminal domain of the glucocorticoid receptor: no association with puerperal psychosis or schizophrenia

Feng, J., Zheng, J., Bennett, W. P., Heston, L. L., Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610 and Sommer, S. S. 2000. Five missense variants in the amino-terminal domain of the glucocorticoid receptor: no association with puerperal psychosis or schizophrenia. American Journal of Medical Genetics 96 (3) , pp. 412-417. 10.1002/1096-8628(20000612)96:3<412::AID-AJMG33>3.0.CO;2-C

Full text not available from this repository.

Abstract

Steroid hormone administration causes behavior changes in many and psychosis in a few. The clinical features suggest that genetic variants of the glucocorticoid receptor or cofactors could produce susceptible subpopulations who react adversely to hormonal cascades. To investigate this possibility, coding and splice site sequences of the glucocorticoid receptor were scanned for single nucleotide polymorphisms in genomic DNA samples from 100 schizophrenics (86 Caucasians and 14 African-Americans) and 40 Caucasians with puerperal psychosis. Five amino acid substitutions were found in the amino-terminal domain at frequencies of 0.6 to 3.8% in Caucasians: R23K, F29L, L112F, D233N, and N363S. In addition, four silent nucleotide changes were found: E22E, K293K, D677D, and N766N; a transversion in intron 4 occurred beyond the splice junction. None of these variants can be linked to these disorders at present. However, the N363S variant contributes a new potential phosphorylation site and has been associated with increased body mass and reduced bone mineral density [Huizenga et al., 1998], so it is possible that the other missense variants confer traits that currently are unrecognized. Comparisons to natural glucocorticoid receptor mutants in the familial glucocorticoid resistance syndrome and steroid resistant leukemias suggest that amino acid substitutions at highly conserved residues may cause severe functional defects and serious illness, while changes at less conserved sites produce lesser alterations and milder disease

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Amino Acid Sequence, Animals, Case-Control Studies, Conserved Sequence, Ethnic Groups, Female, Gene Frequency, Genetic Variation, Humans, Male, Mammals, Middle Aged, Mutation, Missense, Polymorphism, Single-Stranded Conformational, Pregnancy, Protein Structure, Tertiary, Psychotic Disorders/genetics, Puerperal Disorders/genetics, Receptors, Glucocorticoid/chemistry, Receptors, Glucocorticoid/genetics, Schizophrenia/genetics, Transcription, Genetic
Publisher:	Wiley-Liss
ISSN:	0148-7299
Last Modified:	27 Oct 2022 08:53
URI:	https://orca.cardiff.ac.uk/id/eprint/63659

Citation Data

Cited 44 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item