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Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency

BACKGROUND: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease caused by ACTH resistance and leads to isolated glucocorticoid deficiency. Although FGD patients typically have normal mineralocorticoid secretion, subtle alterations in the renin–angiotensin–aldosterone axis...

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Autores principales: Dias, R P, Chan, L F, Metherell, L A, Pearce, S H S, Clark, A J L
Formato: Texto
Lenguaje:English
Publicado: BioScientifica 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808202/
https://www.ncbi.nlm.nih.gov/pubmed/19903795
http://dx.doi.org/10.1530/EJE-09-0720
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author Dias, R P
Chan, L F
Metherell, L A
Pearce, S H S
Clark, A J L
author_facet Dias, R P
Chan, L F
Metherell, L A
Pearce, S H S
Clark, A J L
author_sort Dias, R P
collection PubMed
description BACKGROUND: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease caused by ACTH resistance and leads to isolated glucocorticoid deficiency. Although FGD patients typically have normal mineralocorticoid secretion, subtle alterations in the renin–angiotensin–aldosterone axis have been reported in a subset of patients at presentation. Anecdotally, some patients with FGD have been initially diagnosed as having Addison's disease (AD), with implications for treatment and genetic counselling. Currently, mutations in three genes: the ACTH receptor (MC2R); the melanocortin 2 receptor accessory protein (MRAP); and the steroidogenic acute regulatory protein (STAR) are known to give rise to FGD types 1–3. We investigated a cohort of autoantibody-negative AD patients for mutations in these genes. METHODS: Forty patients with known AD without evidence of autoimmune disease were screened for mutations in MC2R, MRAP and STAR. In addition, patients were genotyped for the MC2R promoter polymorphism previously associated with reduced responsiveness to ACTH. RESULTS: No mutations in MC2R, MRAP or STAR were identified in any patient. The frequencies of the MC2R promoter polymorphism were similar to those reported in healthy controls. CONCLUSIONS: FGD does not appear to be underdiagnosed in the AD population. However, in ∼50% of patients with FGD, no genetic cause has yet been identified and it is possible that the other, as yet unidentified, genes giving rise to FGD may be implicated in AD.
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spelling pubmed-28082022010-02-01 Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency Dias, R P Chan, L F Metherell, L A Pearce, S H S Clark, A J L Eur J Endocrinol Clinical Study BACKGROUND: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease caused by ACTH resistance and leads to isolated glucocorticoid deficiency. Although FGD patients typically have normal mineralocorticoid secretion, subtle alterations in the renin–angiotensin–aldosterone axis have been reported in a subset of patients at presentation. Anecdotally, some patients with FGD have been initially diagnosed as having Addison's disease (AD), with implications for treatment and genetic counselling. Currently, mutations in three genes: the ACTH receptor (MC2R); the melanocortin 2 receptor accessory protein (MRAP); and the steroidogenic acute regulatory protein (STAR) are known to give rise to FGD types 1–3. We investigated a cohort of autoantibody-negative AD patients for mutations in these genes. METHODS: Forty patients with known AD without evidence of autoimmune disease were screened for mutations in MC2R, MRAP and STAR. In addition, patients were genotyped for the MC2R promoter polymorphism previously associated with reduced responsiveness to ACTH. RESULTS: No mutations in MC2R, MRAP or STAR were identified in any patient. The frequencies of the MC2R promoter polymorphism were similar to those reported in healthy controls. CONCLUSIONS: FGD does not appear to be underdiagnosed in the AD population. However, in ∼50% of patients with FGD, no genetic cause has yet been identified and it is possible that the other, as yet unidentified, genes giving rise to FGD may be implicated in AD. BioScientifica 2010-02 /pmc/articles/PMC2808202/ /pubmed/19903795 http://dx.doi.org/10.1530/EJE-09-0720 Text en © 2010 European Society of Endocrinology http://www.bioscientifica.com/journals/reuselicenceeje/ This is an Open Access article distributed under the terms of the European Journal of Endocrinology's Re-use Licence (http://www.bioscientifica.com/journals/reuselicenceeje/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Study
Dias, R P
Chan, L F
Metherell, L A
Pearce, S H S
Clark, A J L
Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency
title Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency
title_full Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency
title_fullStr Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency
title_full_unstemmed Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency
title_short Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency
title_sort isolated addison's disease is unlikely to be caused by mutations in mc2r, mrap or star, three genes responsible for familial glucocorticoid deficiency
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808202/
https://www.ncbi.nlm.nih.gov/pubmed/19903795
http://dx.doi.org/10.1530/EJE-09-0720
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