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Case Report: A Novel ARMC5 Germline Mutation in a Patient with Primary Bilateral Macronodular Adrenal Hyperplasia and Hypogammaglobulinemia

Primary bilateral macronodular adrenal hyperplasia (PBMAH) represents an uncommon cause of endogenous hypercortisolism. Since the first description in 2003 in a French cohort, many papers have been published describing families as well as isolated individuals affected with this condition, who were f...

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Autores principales: Vena, Walter, Morelli, Valentina, Carrabba, Maria, Elli, Francesca, Fabio, Giovanna, Muller, Ilaria, Lucca, Camilla, Maffini, Maria Antonia, Lania, Andrea Gerardo, Mantovani, Giovanna, Arosio, Maura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965228/
https://www.ncbi.nlm.nih.gov/pubmed/35368666
http://dx.doi.org/10.3389/fgene.2022.834067
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author Vena, Walter
Morelli, Valentina
Carrabba, Maria
Elli, Francesca
Fabio, Giovanna
Muller, Ilaria
Lucca, Camilla
Maffini, Maria Antonia
Lania, Andrea Gerardo
Mantovani, Giovanna
Arosio, Maura
author_facet Vena, Walter
Morelli, Valentina
Carrabba, Maria
Elli, Francesca
Fabio, Giovanna
Muller, Ilaria
Lucca, Camilla
Maffini, Maria Antonia
Lania, Andrea Gerardo
Mantovani, Giovanna
Arosio, Maura
author_sort Vena, Walter
collection PubMed
description Primary bilateral macronodular adrenal hyperplasia (PBMAH) represents an uncommon cause of endogenous hypercortisolism. Since the first description in 2003 in a French cohort, many papers have been published describing families as well as isolated individuals affected with this condition, who were found to harbor a genetic variants in the armadillo-repeat containing 5 (ARMC5) gene, a tumor-suppressor gene with a still unknown role in the disease pathogenesis. Studies in rat models suggested a possible link between ARMC5 damaging variants and the impairment of the cell-mediated immune response, leading to a higher susceptibility to bacterial and viral infections. To our knowledge, we describe the first case of a patient affected by PBMAH with hypogammaglobulinemia and monthly relapsing human herpes simplex viral infections. After the detection of subclinical Cushing’s syndrome, a unilateral laparoscopic adrenalectomy was performed. Subsequent genetic analysis of ARMC5 performed on genomic DNA extracted both from the adrenal tissue and lymphocytes revealed a novel somatic frameshift variant in exon 1 (c.231_265del:p.A77Afs*13) and a novel germline variant in exon 6 (c.2436del: p. C813Vfs*104). After adrenalectomy, we observed a significant improvement of clinical features concerning both hypercortisolism and relapsing viral infections, thus suggesting a possible adjuvant role of hypercortisolism on a genetic-based derangement of the immune system.
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spelling pubmed-89652282022-03-31 Case Report: A Novel ARMC5 Germline Mutation in a Patient with Primary Bilateral Macronodular Adrenal Hyperplasia and Hypogammaglobulinemia Vena, Walter Morelli, Valentina Carrabba, Maria Elli, Francesca Fabio, Giovanna Muller, Ilaria Lucca, Camilla Maffini, Maria Antonia Lania, Andrea Gerardo Mantovani, Giovanna Arosio, Maura Front Genet Genetics Primary bilateral macronodular adrenal hyperplasia (PBMAH) represents an uncommon cause of endogenous hypercortisolism. Since the first description in 2003 in a French cohort, many papers have been published describing families as well as isolated individuals affected with this condition, who were found to harbor a genetic variants in the armadillo-repeat containing 5 (ARMC5) gene, a tumor-suppressor gene with a still unknown role in the disease pathogenesis. Studies in rat models suggested a possible link between ARMC5 damaging variants and the impairment of the cell-mediated immune response, leading to a higher susceptibility to bacterial and viral infections. To our knowledge, we describe the first case of a patient affected by PBMAH with hypogammaglobulinemia and monthly relapsing human herpes simplex viral infections. After the detection of subclinical Cushing’s syndrome, a unilateral laparoscopic adrenalectomy was performed. Subsequent genetic analysis of ARMC5 performed on genomic DNA extracted both from the adrenal tissue and lymphocytes revealed a novel somatic frameshift variant in exon 1 (c.231_265del:p.A77Afs*13) and a novel germline variant in exon 6 (c.2436del: p. C813Vfs*104). After adrenalectomy, we observed a significant improvement of clinical features concerning both hypercortisolism and relapsing viral infections, thus suggesting a possible adjuvant role of hypercortisolism on a genetic-based derangement of the immune system. Frontiers Media S.A. 2022-03-15 /pmc/articles/PMC8965228/ /pubmed/35368666 http://dx.doi.org/10.3389/fgene.2022.834067 Text en Copyright © 2022 Vena, Morelli, Carrabba, Elli, Fabio, Muller, Lucca, Maffini, Lania, Mantovani and Arosio. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Vena, Walter
Morelli, Valentina
Carrabba, Maria
Elli, Francesca
Fabio, Giovanna
Muller, Ilaria
Lucca, Camilla
Maffini, Maria Antonia
Lania, Andrea Gerardo
Mantovani, Giovanna
Arosio, Maura
Case Report: A Novel ARMC5 Germline Mutation in a Patient with Primary Bilateral Macronodular Adrenal Hyperplasia and Hypogammaglobulinemia
title Case Report: A Novel ARMC5 Germline Mutation in a Patient with Primary Bilateral Macronodular Adrenal Hyperplasia and Hypogammaglobulinemia
title_full Case Report: A Novel ARMC5 Germline Mutation in a Patient with Primary Bilateral Macronodular Adrenal Hyperplasia and Hypogammaglobulinemia
title_fullStr Case Report: A Novel ARMC5 Germline Mutation in a Patient with Primary Bilateral Macronodular Adrenal Hyperplasia and Hypogammaglobulinemia
title_full_unstemmed Case Report: A Novel ARMC5 Germline Mutation in a Patient with Primary Bilateral Macronodular Adrenal Hyperplasia and Hypogammaglobulinemia
title_short Case Report: A Novel ARMC5 Germline Mutation in a Patient with Primary Bilateral Macronodular Adrenal Hyperplasia and Hypogammaglobulinemia
title_sort case report: a novel armc5 germline mutation in a patient with primary bilateral macronodular adrenal hyperplasia and hypogammaglobulinemia
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965228/
https://www.ncbi.nlm.nih.gov/pubmed/35368666
http://dx.doi.org/10.3389/fgene.2022.834067
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