A novel germline ARMC5 mutation in a patient with bilateral macronodular adrenal hyperplasia: a case report

BACKGROUND: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing’s syndrome (CS). BMAH is predominantly believed to be caused by two mutations, a germline and somatic one, respectively, as described in the two-hit hypothesis. In many familial cases of BMAH, mutations in armad...

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Autores principales: Liu, Qiuli, Tong, Dali, Xu, Jing, Yang, Xingxia, Yi, Yuting, Zhang, Dianzheng, Wang, Luofu, Zhang, Jun, Zhang, Yao, Li, Yaoming, Chang, Lianpeng, Chen, Rongrong, Guan, Yanfang, Yi, Xin, Jiang, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870939/
https://www.ncbi.nlm.nih.gov/pubmed/29587644
http://dx.doi.org/10.1186/s12881-018-0564-2
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author Liu, Qiuli
Tong, Dali
Xu, Jing
Yang, Xingxia
Yi, Yuting
Zhang, Dianzheng
Wang, Luofu
Zhang, Jun
Zhang, Yao
Li, Yaoming
Chang, Lianpeng
Chen, Rongrong
Guan, Yanfang
Yi, Xin
Jiang, Jun
author_facet Liu, Qiuli
Tong, Dali
Xu, Jing
Yang, Xingxia
Yi, Yuting
Zhang, Dianzheng
Wang, Luofu
Zhang, Jun
Zhang, Yao
Li, Yaoming
Chang, Lianpeng
Chen, Rongrong
Guan, Yanfang
Yi, Xin
Jiang, Jun
author_sort Liu, Qiuli
collection PubMed
description BACKGROUND: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing’s syndrome (CS). BMAH is predominantly believed to be caused by two mutations, a germline and somatic one, respectively, as described in the two-hit hypothesis. In many familial cases of BMAH, mutations in armadillo repeat containing 5 (ARMC5), a putative tumor suppressor gene, are thought to induce the disorder. The objective of this study was to report a case in which the patient presented with BMAH induced by a novel heterozygous germline ARMC5 mutation (c. 517C > T, p. Arg173*) alone rather than a two-hit mutation. CASE PRESENTATION: A 51-year-old woman was identified with masses in the bilateral adrenals. Serum cortisol levels were increased significantly both in the morning (08:00 AM) and late at night (24:00 AM), while plasma adrenocorticotropic hormone was normal. The patient underwent a left adrenalectomy and histopathology substantiated the BMAH diagnosis. WES of the germline DNA discovered a novel heterozygous germline ARMC5 mutation (c. 517C > T, p. Arg173*) and in silico analysis predicted that the mutation significantly impaired protein function, resulting in inactivated ARMC5. Subsequently, WES of the tumor specimen identified 79 somatic single nucleotide polymorphisms (SNPs)/insertion-deletion (indel) mutations, including 32 missense/nonsense/splice/stop-loss mutations. None of these mutations were CS-related. CONCLUSIONS: A novel germline ARMC5 mutation (c. 517C > T, p. Arg173*) was identified that induced BMAH alone without a second mutation. ARMC5 sequencing may improve the identification of clinical forms of BMAH and allow earlier diagnosis of this disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0564-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-58709392018-04-02 A novel germline ARMC5 mutation in a patient with bilateral macronodular adrenal hyperplasia: a case report Liu, Qiuli Tong, Dali Xu, Jing Yang, Xingxia Yi, Yuting Zhang, Dianzheng Wang, Luofu Zhang, Jun Zhang, Yao Li, Yaoming Chang, Lianpeng Chen, Rongrong Guan, Yanfang Yi, Xin Jiang, Jun BMC Med Genet Case Report BACKGROUND: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing’s syndrome (CS). BMAH is predominantly believed to be caused by two mutations, a germline and somatic one, respectively, as described in the two-hit hypothesis. In many familial cases of BMAH, mutations in armadillo repeat containing 5 (ARMC5), a putative tumor suppressor gene, are thought to induce the disorder. The objective of this study was to report a case in which the patient presented with BMAH induced by a novel heterozygous germline ARMC5 mutation (c. 517C > T, p. Arg173*) alone rather than a two-hit mutation. CASE PRESENTATION: A 51-year-old woman was identified with masses in the bilateral adrenals. Serum cortisol levels were increased significantly both in the morning (08:00 AM) and late at night (24:00 AM), while plasma adrenocorticotropic hormone was normal. The patient underwent a left adrenalectomy and histopathology substantiated the BMAH diagnosis. WES of the germline DNA discovered a novel heterozygous germline ARMC5 mutation (c. 517C > T, p. Arg173*) and in silico analysis predicted that the mutation significantly impaired protein function, resulting in inactivated ARMC5. Subsequently, WES of the tumor specimen identified 79 somatic single nucleotide polymorphisms (SNPs)/insertion-deletion (indel) mutations, including 32 missense/nonsense/splice/stop-loss mutations. None of these mutations were CS-related. CONCLUSIONS: A novel germline ARMC5 mutation (c. 517C > T, p. Arg173*) was identified that induced BMAH alone without a second mutation. ARMC5 sequencing may improve the identification of clinical forms of BMAH and allow earlier diagnosis of this disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0564-2) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-27 /pmc/articles/PMC5870939/ /pubmed/29587644 http://dx.doi.org/10.1186/s12881-018-0564-2 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Liu, Qiuli
Tong, Dali
Xu, Jing
Yang, Xingxia
Yi, Yuting
Zhang, Dianzheng
Wang, Luofu
Zhang, Jun
Zhang, Yao
Li, Yaoming
Chang, Lianpeng
Chen, Rongrong
Guan, Yanfang
Yi, Xin
Jiang, Jun
A novel germline ARMC5 mutation in a patient with bilateral macronodular adrenal hyperplasia: a case report
title A novel germline ARMC5 mutation in a patient with bilateral macronodular adrenal hyperplasia: a case report
title_full A novel germline ARMC5 mutation in a patient with bilateral macronodular adrenal hyperplasia: a case report
title_fullStr A novel germline ARMC5 mutation in a patient with bilateral macronodular adrenal hyperplasia: a case report
title_full_unstemmed A novel germline ARMC5 mutation in a patient with bilateral macronodular adrenal hyperplasia: a case report
title_short A novel germline ARMC5 mutation in a patient with bilateral macronodular adrenal hyperplasia: a case report
title_sort novel germline armc5 mutation in a patient with bilateral macronodular adrenal hyperplasia: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870939/
https://www.ncbi.nlm.nih.gov/pubmed/29587644
http://dx.doi.org/10.1186/s12881-018-0564-2
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