Zhang Y, Tao Y, Wu Q, Liu X, Zou C, Geng H
Department of Endocrine, Xuzhou Central Hospital, Xuzhou, China.
Department of Endocrine, Xuzhou Medical University, Xuzhou, China.
Acta Endocrinol (Buchar). 2024 Jul-Sep;20(3):277-285. doi: 10.4183/aeb.2024.277. Epub 2025 May 23.
ARMC5 mutations are responsible for the development of primary bilateral macronodular adrenal hyperplasia (PBMAH). In this study, we aimed to report a novel ARMC5 germline variant in a PBMAH patient family.
CT examination and dexamethasone suppression test (DST) were used in the diagnosis of PBMAH. Sanger sequencing was used to validate the familial heredity. For the novel variant, protein predictive analysis was performed to study the changes of secondary and tertiary structures and hydrophobicity.
A 45 years old male (proband, III-1) was diagnosed as PBMAH. Whole-exome sequencing (WES) was performed, finding one mutation: c.719_ 724dup, p Arg240_ Pro241dup. Sanger sequencing showed the II-2, III-1, IV-1 with heterozygous gene, confirming the familial heredity. For protein predictive analysis, the predicted secondary structure of variants has one alpha-helix structure incomplete compared with normal ARMC5. The tertiary structure could draw the same conclusion, that hydrophobicity decreases after mutation.
We reported a new-found ARMC5 germline variant in PBMAH using WES and protein predictive analysis. With the help of WES, early diagnosis of PBMAH could help variant carriers to prevent the occurrence of cancer by lifetime follow-up.
ARMC5突变是原发性双侧大结节性肾上腺增生（PBMAH）发病的原因。在本研究中，我们旨在报告一个PBMAH患者家族中的一种新的ARMC5种系变体。
采用CT检查和地塞米松抑制试验（DST）诊断PBMAH。采用桑格测序法验证家族遗传性。对于新变体，进行蛋白质预测分析以研究二级和三级结构以及疏水性的变化。
一名45岁男性（先证者，III-1）被诊断为PBMAH。进行了全外显子组测序（WES），发现一个突变：c.719_724dup，p.Arg240_Pro241dup。桑格测序显示II-2、III-1、IV-1为杂合基因，证实了家族遗传性。对于蛋白质预测分析，与正常ARMC5相比，变体的预测二级结构有一个α-螺旋结构不完整。三级结构也能得出相同结论，即突变后疏水性降低。
我们通过WES和蛋白质预测分析报告了PBMAH中一种新发现的ARMC5种系变体。借助WES，PBMAH的早期诊断有助于变体携带者通过终身随访预防癌症的发生。
