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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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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. |
format | Online Article Text |
id | pubmed-5870939 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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