Novel pathogenic variations of the armadillo repeat-containing protein 5 gene in patients with primary bilateral macronodular adrenal hyperplasia

Gao Fei; Bian Zhiying; Zhu Boyu; Xiao Haiying; Wang Yi; Wang Hongyu; Xu Chun

doi:10.13406/j.cnki.cyxb.003953

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Novel pathogenic variations of the armadillo repeat-containing protein 5 gene in patients with primary bilateral macronodular adrenal hyperplasia

Endocrine regulation and metabolic diseases\—hereditary endocrine and metabolic diseases | 更新时间：2026-10-26

- Novel pathogenic variations of the armadillo repeat-containing protein 5 gene in patients with primary bilateral macronodular adrenal hyperplasia
- Journal of Chongqing Medical University Vol. 51, Issue 10, Pages: 1370-1376(2026)
- 作者机构：
  
  中国人民解放军总医院第三医学中心内分泌科，北京 100039
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003953
  CLC： R586
- Received：05 June 2025，
  
  Revised：2025-08-08，
  
  Accepted：27 August 2025，
  
  Published：28 October 2026
- 稿件说明：
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高飞,边志颖,朱泊羽等.原发性双侧大结节性肾上腺皮质增生患者ARMC5基因新的致病变异[J].重庆医科大学学报,2026,51(10):1370-1376.

Gao Fei,Bian Zhiying,Zhu Boyu,et al.Novel pathogenic variations of the armadillo repeat-containing protein 5 gene in patients with primary bilateral macronodular adrenal hyperplasia[J].Journal of Chongqing Medical University,2026,51(10):1370-1376.
高飞,边志颖,朱泊羽等.原发性双侧大结节性肾上腺皮质增生患者ARMC5基因新的致病变异[J].重庆医科大学学报,2026,51(10):1370-1376. DOI： 10.13406/j.cnki.cyxb.003953.

Gao Fei,Bian Zhiying,Zhu Boyu,et al.Novel pathogenic variations of the armadillo repeat-containing protein 5 gene in patients with primary bilateral macronodular adrenal hyperplasia[J].Journal of Chongqing Medical University,2026,51(10):1370-1376. DOI： 10.13406/j.cnki.cyxb.003953.

摘要

目的

对原发性双侧大结节性肾上腺皮质增生（primary bilateral macronodular adrenal hyperplasia

，PBMAH）患者进行含犰狳重复序列蛋白5（armadillo repeat containing 5，

ARMC5

）基因种系致病变异的遗传筛查和分析。

方法

对2024年5月至2024年10月于解放军总医院第三医学中心内分泌科就诊的3例PBMAH患者进行全外显子组基因检测，并在携带

ARMC5

变异的受试者中进行了家系分析。

结果

通过全外显子组测序在3例PBMAH患者中均检测到

ARMC5

基因的杂合种系变异。其中c.622dup（p.Gln208ProfsTer15）为已知的致病变异；另2种变异位点c.814dup（p.Ala272GlyfsTer4）、c.2663_2680delinsGGAAGCGG（p.Thr888ArgfsTer26）为新发变异位点，二者均为无效变异（移码突变），可能导致基因功能丧失，同时未在人类遗传变异数据库或gnomAD数据库中收录，结合患者的临床表现及内分泌功能试验指标倾向于致病性变异。

结论

ARMC5

基因突变是PBMAH常见的原因，对散发性PBMAH患者进行基因检测非常重要，有助于建立疾病基因型-表型关联，为临床决策提供可靠的分子诊断依据。

Abstract

Objective

To perform the genetic screening and analysis of pathogenic germline variations of the armadillo repeat-containing protein 5（

ARMC5

） gene in patients with primary bilateral macronodular adrenal hyperplasia（PBMAH）.

Methods

Whole exome genetic testing was performed for three PBMAH patients who attended Department of Endocrinology，The Third Medical Center of Chinese PLA General Hospital，from May to October 2024，and a family analysis was performed for the subjects with

ARMC5

mutation.

Results

Heterozygous germline variations of the

ARMC5

gene were identified by whole-exome sequencing in all three patients with PBMAH. Among these variations，c.622dup（p.glin208Profster15） was a known pathogenic variation，and the other two variation sites，c.814dup（p.Al272Glyfster4） and c.2663_2680delinsGGAAGCGG（p.TR888Argfster26），were novel variation sites，both of which were null mutations（frameshift mutation） and might lead to the loss of gene function. In addition，these two variations were not found in the human genetic variation database or the gnomAD database，and based on the clinical manifestations and endocrine function indicators of the patients，they were likely to be path

ogenic variations.

Conclusion

ARMC5

gene mutation is a common cause of PBMAH. Genetic testing is of great importance for patients with sporadic PBMAH and can help to establish the genotype-phenotype association of the disease and provide a reliable molecular diagnostic basis for clinical decision-making.

关键词

Keywords

references

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