A novel germline ARMC5 mutation in a patient with bilateral macronodular adrenal hyperplasia: a case report

作者：Liu, Qiuli; Tong, Dali; Xu, Jing; Yang, Xingxia; Yi, Yuting; Zhang, Dianzheng; Wang, Luofu; Zhang, Jun; Zhang, Yao; Li, Yaoming; Chang, Lianpeng; Chen, Rongrong; Guan, Yanfang; Yi, Xin; Jiang, Jun^*

来源：BMC Medical Genetics, 2018, 19(1): 49.

DOI：10.1186/s12881-018-0564-2

• Bilateral macronodular adrenal hyperplasia
• Cushing's syndrome
• ARMC5

Background: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing's syndrome (CS). BMAH is predominantly believed to be caused by two mutations, a germline and somatic one, respectively, as described in the two-hit hypothesis. In many familial cases of BMAH, mutations in armadillo repeat containing 5 (ARMC5), a putative tumor suppressor gene, are thought to induce the disorder. The objective of this study was to report a case in which the patient presented with BMAH induced by a novel heterozygous germline ARMC5 mutation (c.517C > T, p.Arg173*) alone rather than a two-hit mutation.
Case presentation: A 51-year-old woman was identified with masses in the bilateral adrenals. Serum cortisol levels were increased significantly both in the morning (08:00 AM) and late at night (24:00 AM), while plasma adrenocorticotropic hormone was normal. The patient underwent a left adrenalectomy and histopathology substantiated the BMAH diagnosis. WES of the germline DNA discovered a novel heterozygous germline ARMC5 mutation (c. 517C > T, p.Arg173*) and in silico analysis predicted that the mutation significantly impaired protein function, resulting in inactivated ARMC5. Subsequently, WES of the tumor specimen identified 79 somatic single nucleotide polymorphisms (SNPs)/insertion-deletion (indel) mutations, including 32 missense/nonsense/splice/stop-loss mutations. None of these mutations were CS-related.
Conclusions: A novel germline ARMC5 mutation (c. 517C > T, p.Arg173*) was identified that induced BMAH alone without a second mutation. ARMC5 sequencing may improve the identification of clinical forms of BMAH and allow earlier diagnosis of this disease.

• 出版日期2018-3-27
• 单位中国人民解放军陆军军医大学