CoChat
Sign Up
Cited by 121Adrenal and Paraganglionic TumorsAdrenal Hormones and DisordersPituitary Gland Disorders and Treatments

ARMC5 Mutations Are Common in Familial Bilateral Macronodular Adrenal Hyperplasia

Gagliardi, Lucia, Schreiber, Andreas W., Hahn, Christopher N., Feng, Jinghua, Cranston, Treena, Boon, Hannah, Hotu, Cheri, Oftedal, Bergithe E. +8 more·2014·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2014-1265
Open this paper in CoChat — free account

Abstract

CONTEXT: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare form of adrenal Cushing's syndrome. Familial cases have been reported, but at the time we conducted this study, the genetic basis of BMAH was unknown. Recently, germline variants of armadillo repeat containing 5 (ARMC5) in patients with isolated BMAH and somatic, second-hit mutations in tumor nodules, were identified. OBJECTIVE: Our objective was to identify the genetic basis of familial BMAH. DESIGN: We performed whole exome capture and sequencing of 2 affected individuals from each of 4 BMAH families (BMAH-01, BMAH-02, BMAH-03, and BMAH-05). Based on clinical evaluation, there were 7, 3, 3, and 4 affected individuals in these families, respectively. Sanger sequencing of ARMC5 was performed in 1 other BMAH kindred, BMAH-06. RESULTS: Exome sequencing identified novel variants Chr16:g.31477540, c.2139delT, p.(Thr715Leufs*1) (BMAH-02) and Chr16:g.31473811, c.943C→T, p.(Arg315Trp) (BMAH-03) in ARMC5 (GRch37/hg19), validated by Sanger sequencing. BMAH-01 had a recently reported mutation Chr16:g.31476121, c.1777C→T, p.(Arg593Trp). Sanger sequencing of ARMC5 in BMAH-06 identified a previously reported mutation, Chr16:g. 31473688; c.799C→T, p.(Arg267*). The genetic basis of BMAH in BMAH-05 was not identified. CONCLUSIONS: Our studies have detected ARMC5 mutations in 4 of 5 BMAH families tested, confirming that these mutations are a frequent cause of BMAH. Two of the 4 families had novel mutations, indicating allelic heterogeneity. Preclinical evaluation did not predict mutation status. The ARMC5-negative family had unusual prominent hyperaldosteronism. Further studies are needed to determine the penetrance of BMAH in ARMC5 mutation-positive relatives of affected patients, the practical utility of genetic screening and genotype-phenotype correlations.

Integrity signals

Registry

Crossref · 10.1210/jc.2014-1265

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Patients with ARMC5 mutations tend to display adrenal hyperplasia associated with multiple nodules.

    “Patients with ARMC5 mutations tend to display adrenal hyperplasia associated with multiple nodules (172-175).”

    From Adrenal incidentaloma (2020) · cites this paper as [173]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Gagliardi, L., Schreiber, A. W., Hahn, C. N., Feng, J., Cranston, T., Boon, H., Hotu, C., Oftedal, B. E., Cutfield, R., Adelson, D. L., Braund, W. J., Gordon, R. D., Rees, D. A., Grossman, A. B., Torpy, D. J., & Scott, H. S.
Affiliations
  • Royal Adelaide Hospital (AU)
  • South Australia Pathology (AU)
  • Department of Genetics and Molecular Pathology (L.G., C.N.H., B.E.O., H.S.S.), Adelaide SA 5000, Australia
  • Oxford Medical Genetics Laboratories (T.C., H.B.), Oxford OX3 7LE, United Kingdom
  • Greenlane Clinical Centre (NZ)
  • University of Bergen (NO)
  • North Shore Hospital (NZ)
  • The University of Adelaide (AU)
  • Flinders Medical Centre (AU)
  • The University of Queensland (AU)
  • Centre for Endocrine and Diabetes Sciences (D.A.R.), School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom
  • National Health Service (GB)
Corresponding author
Gagliardi, Lucia
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2014-09-01
Volume
99
Issue
9
Pages
E1784-E1792
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2014-1265
OpenAlex
W1993251688
Cited by
121
References
34
Citations by year
2026: 4 · 2025: 7 · 2024: 8 · 2023: 10 · 2022: 9 · 2021: 9 · 2020: 13 · 2019: 8 · 2018: 10 · 2017: 10 · 2016: 11 · 2015: 15 · 2014: 7
FWCI
14.19
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords
bilateral macronodular adrenal hyperplasia, adrenal Cushing's syndrome, germline mutations, novel mutations, allelic heterogeneity, hyperaldosteronism, penetrance, loss-of-function mutations, second-hit mutations, tumor nodules, exome sequencing, Sanger sequencing validation
MeSH terms
Adrenal Hyperplasia, Congenital, Adult, Aged, Base Sequence, Cushing Syndrome, Family Health, Female, Humans, Male, Middle Aged, Molecular Sequence Data, Phenotype, Germ-Line Mutation, Tumor Suppressor Proteins, Armadillo Domain Proteins, Genome-Wide Association Study, Exome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review