Allelic Variants of ARMC5 in Patients With Adrenal Incidentalomas and in Patients With Cushing's Syndrome Associated With Bilateral Adrenal Nodules

Mariani, Beatriz Marinho de Paula; Nishi, Mirian Yumie; Wanichi, Ingrid Quevedo; Brondani, Vânia Balderrama; Lacombe, Amanda Meneses Ferreira; Charchar, Helaine Laiz Silva; Pereira, Maria Adelaide Albergaria; Srougi, Victor; Tanno, Fabio Y; Ceccato, Filippo; Regazzo, Daniela; Barbot, Mattia; Occhi, Gianluca; Albiger, Nora; Vieira-Corrêa, Marcelo; Kater, Cláudio E.; Scaroni, Carla; Chambô, José Luis; Zerbini, Maria Cláudia Nogueira; Mendonça, Berenice Bilharinho; Almeida, Madson Q.; Fragoso, Maria Candida Barisson Villares

doi:10.3389/fendo.2020.00036

Cited by 10 publications

(8 citation statements)

References 19 publications

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“…The genetic analysis detected the know germline variant of ARMc5 gene c.968G > A, resulting in a substitution of a Glycine in Aspartate at codon 323 this variant has been reported by Mariani and has been classified as a variant of uncertain significance (Mariani et al, 2020 ) (Table 3 ). For this patient, it was possible to search for the second hit at the somatic level: genetic analysis of the tumor tissue showed the presence of a deleterious frameshift variant: p.Leu676Trp fs*13 .…”

Section: Resultsmentioning

confidence: 82%

“…The replacement of a Glycine (a sterically simple non‐polar amino acid) with an Aspartic Acid (polar amino acid negatively charged due to the presence of a –CH 2 COO − ) which is a bulky amino acid could lead to a substantial alteration of the structure of the protein. The p.Gly323Asp variant reported by Mariani (Mariani et al, 2020 ) was classified as likely disease‐causing pathologic variant (VUS class III), the identification of a deleterious variant in tumor sample allows the reclassification of the variant to a pathogenetic class (VUS class IV‐V). The bioinformatic tools, that we used for the evaluation of the potential pathogenicity of variants, give consistent results, all conferring a possible damaging effect on the two new variants, however, in silico analysis could be considered a preliminary approach.…”

Section: Discussionmentioning

confidence: 99%

“… b PM2: absent from controls, all variants were checked in the Exome Aggregation Consortium Database (Exac). c PP3: Multiple lines of computational evidence support a deleterious effect on the gene or gene product (Annex Table 2 , Mariani et al, 2020 ). …”

Section: Methodsmentioning

confidence: 99%

“… c PP3: Multiple lines of computational evidence support a deleterious effect on the gene or gene product (Annex Table 2 , Mariani et al, 2020 ). …”

Section: Methodsmentioning

confidence: 99%

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New pathogenic variants in ARMC5 gene in a series of Italian patients affected by primary bilateral macronodular adrenocortical hyperplasia (PBMAH)

Giacchè

Panarotto

Mori

et al. 2023

Molec Gen & Gen Med

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Background To perform genetic screening for ARMC5 gene germline pathogenic variants in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH). Subjects and Methods In a group of 10 PBMAH patients, we performed complete sequencing of the coding region of the ARMC5 gene and MLPA analysis for large deletion detection. In subjects with the ARMC5 variant, we searched ARMC5 gene somatic variants on tumor samples. Results Among 10 PBMAH patients, we identified four ARMC5 germline variants (40%). One variant, c:174dupC p.Glu59Argfs*44, was already known; one variant p.Gly323Asp, was already reported and classified as likely disease‐causing VUS (class 3–4); two variants p.Leu596Arg and p.Arg811Pro, were never reported before. For p.Gly323Asp and p.Arg811Pro, we identified second deleterious variants at the somatic level, enforcing the possible pathogenic effect of germline variants. Conclusions Our results underscore the importance of performing genetic testing also in sporadic PBMAH patients and broaden the spectrum of molecular variants involved in PBMAH syndrome.

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Section: Resultsmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“… c PP3: Multiple lines of computational evidence support a deleterious effect on the gene or gene product (Annex Table 2 , Mariani et al, 2020 ). …”

Section: Methodsmentioning

confidence: 99%

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New pathogenic variants in ARMC5 gene in a series of Italian patients affected by primary bilateral macronodular adrenocortical hyperplasia (PBMAH)

Giacchè

Panarotto

Mori

et al. 2023

Molec Gen & Gen Med

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“…Non-pathogenic allelic variants of ARMC5 have also been discovered in unilateral functional and non-functional adrenal nodules. However, ARMC5 association with myelolipomas or mixed tumors has not been reported [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Allelic Variant of Armadillo Repeat Containing Protein 5 (ARMC5) in Myelolipoma Mimicking Pheochromocytoma: A Case Report

Naser¹,

Nava²,

Khosla³

et al. 2023

Cureus

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Adrenal myelolipomas are benign adrenocortical tumors composed of adipose tissue mixed with hematopoietic precursor cells. An association of myelolipoma with adrenal cortical adenoma is rare and the pathogenesis of these tumors remains unclear. Here we present a case of an incidentally discovered adrenal tumor with radiologic characteristics of a myelolipoma who underwent adrenalectomy due to biochemical suspicion for pheochromocytoma. The final pathology, however, revealed a myelolipoma with a co-existing adrenal cortical adenoma without evidence of pheochromocytoma. Genetic analysis revealed the presence of a hitherto unreported heterozygous variant, c.329C>A (p.Ala110Asp), of the armadillo repeat-containing protein 5 (ARMC5) gene which when inactivated is commonly associated with bilateral adrenal nodularity.

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High prevalence of adrenal cortical adenomas in patients with cerebral meningiomas

Filippo

Marca

Losa

et al. 2022

J Endocrinol Invest

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Purpose Adrenal cortical adenomas (ACAs) represent one of the most common endocrine neoplasms. Recently, a genetic syndrome, characterized by tumor-suppressor ARMC5-gene mutations and causing primary macronodular bilateral adrenal hyperplasia with concomitant meningiomas of the central nervous system, has been described. Apart from this rare disorder and despite the well-known influence of steroid hormones on meningiomas, no data are available about the association between ACAs and meningiomas. Methods We investigated the prevalence of ACAs in a group of patients with cerebral meningioma undergoing unenhanced chest CT scans before attending surgical treatment. Patients with meningioma were age- and sex-matched in a 1:3 ratio with hospitalized patients for COVID-19. Results Fifty-six patients with meningioma were included and matched with 168 control patients with COVID-19. One-hundred forty-four (66.1%) were female and the median age was 63 years. Twenty ACAs were detected in the overall population (8.9% of the subjects): 10 in patients with meningioma (18%) and the remaining 10 (6%) in the control group ( p = 0.007). Multivariate analysis showed that age and presence of meningioma were statistically associated with the presence of ACAs ( p = 0.01, p = 0.008). Conclusion We report, for the first time, a higher prevalence of ACAs in patients with meningioma as compared to age- and sex-matched controls. Larger studies are needed to confirm our data and to clarify the characteristics of the ACAs in patients with meningioma. Whether the detection of ACAs should prompt a neuroimaging evaluation to exclude the presence of meningiomas needs also to be considered.

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Allelic Variants of ARMC5 in Patients With Adrenal Incidentalomas and in Patients With Cushing's Syndrome Associated With Bilateral Adrenal Nodules

Cited by 10 publications

References 19 publications

New pathogenic variants in ARMC5 gene in a series of Italian patients affected by primary bilateral macronodular adrenocortical hyperplasia (PBMAH)

New pathogenic variants in ARMC5 gene in a series of Italian patients affected by primary bilateral macronodular adrenocortical hyperplasia (PBMAH)

Allelic Variant of Armadillo Repeat Containing Protein 5 (ARMC5) in Myelolipoma Mimicking Pheochromocytoma: A Case Report

High prevalence of adrenal cortical adenomas in patients with cerebral meningiomas

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