Novel corticosteroid-binding globulin variant that lacks steroid binding activityCitation formats

  • External authors:
  • C. Underhill
  • D. E. Henley
  • K. D. Hadfield
  • W. G. Newman
  • S. L. Lightman
  • G. L. Hammond
  • Peter J. Trainer

Standard

Novel corticosteroid-binding globulin variant that lacks steroid binding activity. / Perogamvros, I.; Underhill, C.; Henley, D. E.; Hadfield, K. D.; Newman, W. G.; Ray, D. W.; Lightman, S. L.; Hammond, G. L.; Trainer, Peter J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 95, No. 10, 10.2010, p. E142-E150.

Research output: Contribution to journalArticlepeer-review

Harvard

Perogamvros, I, Underhill, C, Henley, DE, Hadfield, KD, Newman, WG, Ray, DW, Lightman, SL, Hammond, GL & Trainer, PJ 2010, 'Novel corticosteroid-binding globulin variant that lacks steroid binding activity', Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 10, pp. E142-E150. https://doi.org/10.1210/jc.2010-0746, https://doi.org/10.1210/jc.2010-0746

APA

Perogamvros, I., Underhill, C., Henley, D. E., Hadfield, K. D., Newman, W. G., Ray, D. W., Lightman, S. L., Hammond, G. L., & Trainer, P. J. (2010). Novel corticosteroid-binding globulin variant that lacks steroid binding activity. Journal of Clinical Endocrinology and Metabolism, 95(10), E142-E150. https://doi.org/10.1210/jc.2010-0746, https://doi.org/10.1210/jc.2010-0746

Vancouver

Perogamvros I, Underhill C, Henley DE, Hadfield KD, Newman WG, Ray DW et al. Novel corticosteroid-binding globulin variant that lacks steroid binding activity. Journal of Clinical Endocrinology and Metabolism. 2010 Oct;95(10):E142-E150. https://doi.org/10.1210/jc.2010-0746, https://doi.org/10.1210/jc.2010-0746

Author

Perogamvros, I. ; Underhill, C. ; Henley, D. E. ; Hadfield, K. D. ; Newman, W. G. ; Ray, D. W. ; Lightman, S. L. ; Hammond, G. L. ; Trainer, Peter J. / Novel corticosteroid-binding globulin variant that lacks steroid binding activity. In: Journal of Clinical Endocrinology and Metabolism. 2010 ; Vol. 95, No. 10. pp. E142-E150.

Bibtex

@article{84fafa35f5184fe39e3ffb2f202b737a,
title = "Novel corticosteroid-binding globulin variant that lacks steroid binding activity",
abstract = "Background: Corticosteroid-binding globulin (CBG) is the principal carrier for glucocorticoids in the circulation and a regulator of their bioavailability. Inherited CBG deficiencies are rarely reported, and only three causative mutations in four families have been described. Patients, Methods, and Results: In a 26-yr-old female with hypotension, fatigue, and undetectable total serum cortisol at presentation,wehave identified a novel homozygous c.776g>t transversion in exon 3 of the CBG (SERPINA6) gene. This results in a p.Gly237Val substitution that is predicted to influence the positioning of two β-sheets that constitute part of the CBG steroid-binding site. Two siblings were also homozygous for the variant, whereas her mother and an unaffected sibling were heterozygous. No other symptomatic family members were identified apart from the proband. Individuals homozygous for the variant had serum CBG levels below the reference range when measured by RIA, but CBG was unmeasurable in cortisol-binding capacity assays. In the same individuals, we observed very low baseline and stimulated total serum cortisol levels but normal free serum and salivary cortisol and plasma ACTH. In a study of ultradian cortisol pulsatility, increased pulse frequency was only observed in the proband. Conclusion: We describe a novel CBG variant that lacks steroid binding activity. All mutant homozygotes have very low total serum cortisol, but normal free serum cortisol levels. The only biochemical feature to distinguish the symptomatic subject was increased cortisol pulsatility, and we suggest that this may influence glucocorticoid signaling and contribute to symptoms previously associated with CBG deficiency. Copyright {\textcopyright} 2010 by The Endocrine Society.",
author = "I. Perogamvros and C. Underhill and Henley, {D. E.} and Hadfield, {K. D.} and Newman, {W. G.} and Ray, {D. W.} and Lightman, {S. L.} and Hammond, {G. L.} and Trainer, {Peter J.}",
note = "MOP 143961, Canadian Institutes of Health Research, Canada",
year = "2010",
month = oct,
doi = "10.1210/jc.2010-0746",
language = "English",
volume = "95",
pages = "E142--E150",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Endocrine Society",
number = "10",

}

RIS

TY - JOUR

T1 - Novel corticosteroid-binding globulin variant that lacks steroid binding activity

AU - Perogamvros, I.

AU - Underhill, C.

AU - Henley, D. E.

AU - Hadfield, K. D.

AU - Newman, W. G.

AU - Ray, D. W.

AU - Lightman, S. L.

AU - Hammond, G. L.

AU - Trainer, Peter J.

N1 - MOP 143961, Canadian Institutes of Health Research, Canada

PY - 2010/10

Y1 - 2010/10

N2 - Background: Corticosteroid-binding globulin (CBG) is the principal carrier for glucocorticoids in the circulation and a regulator of their bioavailability. Inherited CBG deficiencies are rarely reported, and only three causative mutations in four families have been described. Patients, Methods, and Results: In a 26-yr-old female with hypotension, fatigue, and undetectable total serum cortisol at presentation,wehave identified a novel homozygous c.776g>t transversion in exon 3 of the CBG (SERPINA6) gene. This results in a p.Gly237Val substitution that is predicted to influence the positioning of two β-sheets that constitute part of the CBG steroid-binding site. Two siblings were also homozygous for the variant, whereas her mother and an unaffected sibling were heterozygous. No other symptomatic family members were identified apart from the proband. Individuals homozygous for the variant had serum CBG levels below the reference range when measured by RIA, but CBG was unmeasurable in cortisol-binding capacity assays. In the same individuals, we observed very low baseline and stimulated total serum cortisol levels but normal free serum and salivary cortisol and plasma ACTH. In a study of ultradian cortisol pulsatility, increased pulse frequency was only observed in the proband. Conclusion: We describe a novel CBG variant that lacks steroid binding activity. All mutant homozygotes have very low total serum cortisol, but normal free serum cortisol levels. The only biochemical feature to distinguish the symptomatic subject was increased cortisol pulsatility, and we suggest that this may influence glucocorticoid signaling and contribute to symptoms previously associated with CBG deficiency. Copyright © 2010 by The Endocrine Society.

AB - Background: Corticosteroid-binding globulin (CBG) is the principal carrier for glucocorticoids in the circulation and a regulator of their bioavailability. Inherited CBG deficiencies are rarely reported, and only three causative mutations in four families have been described. Patients, Methods, and Results: In a 26-yr-old female with hypotension, fatigue, and undetectable total serum cortisol at presentation,wehave identified a novel homozygous c.776g>t transversion in exon 3 of the CBG (SERPINA6) gene. This results in a p.Gly237Val substitution that is predicted to influence the positioning of two β-sheets that constitute part of the CBG steroid-binding site. Two siblings were also homozygous for the variant, whereas her mother and an unaffected sibling were heterozygous. No other symptomatic family members were identified apart from the proband. Individuals homozygous for the variant had serum CBG levels below the reference range when measured by RIA, but CBG was unmeasurable in cortisol-binding capacity assays. In the same individuals, we observed very low baseline and stimulated total serum cortisol levels but normal free serum and salivary cortisol and plasma ACTH. In a study of ultradian cortisol pulsatility, increased pulse frequency was only observed in the proband. Conclusion: We describe a novel CBG variant that lacks steroid binding activity. All mutant homozygotes have very low total serum cortisol, but normal free serum cortisol levels. The only biochemical feature to distinguish the symptomatic subject was increased cortisol pulsatility, and we suggest that this may influence glucocorticoid signaling and contribute to symptoms previously associated with CBG deficiency. Copyright © 2010 by The Endocrine Society.

UR - https://www.mendeley.com/catalogue/eb9e737c-c98c-3120-a204-b3ecec05406c/

U2 - 10.1210/jc.2010-0746

DO - 10.1210/jc.2010-0746

M3 - Article

C2 - 20610591

VL - 95

SP - E142-E150

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 10

ER -