Primary macronodular adrenal hyperplasia (PMAH) can be generated by a new ARMC5 germline variant (c.52C>T (p.Gln18X))

Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing syndrome (CS). In many cases of the PMAH family, variant in ARMC5, a putative tumor suppressor gene, are thought to induce the disease. The purpose of this study was to report a large Chinese family, in which a new germline heterozygous variant of ARMC5 (c.52C>T (p.Gln18X)) was found. A 64-year-old female patient (proband) was admitted to the hospital due to bilateral adrenal masses. In order to clarify the nature and function of adrenal masses, the proband completed several relevant screening tests of the adrenal function. After an ectopic receptor screening test and genetic testing, a new ARMC5 gene variant was found that might had led to the occurrence of PMAH. Because of its characteristic of autosomal dominant inheritance, the proband's relatives were recommended to conduct the genetic test. We collected the family members' genetic information, in which have 27 individuals, the proband tested the whole exon sequence, and 12 participants tested the Sanger sequence. Finally, 7 individuals were found have the same germline variant of ARMC5 as the proband. Subsequent computer analysis predicted that the variant significantly impaired protein function and resulted in inactivation of ARMC5. We found a new germline ARMC5 variant (c.52C>T (p.Gln18X)), which may induced PMAH. ARMC5 sequencing can improve the identification of clinical forms of PMAH and allow early diagnosis of the disease.