부산대학교 도서관

Background: Primary macronodular adrenocortical hyperplasia (PMAH) is a rare form of adrenal Cushing's syndrome with incomplete penetrance which may be sporadic or autosomal dominant. The inactivation of the ARMC5 gene, a potential tumor suppressor gene, is one of the associated causes of PMAH. This study aimed to identify the variant responsible for Iranian familial PMAH. Methods: The proband, a 44-year-old woman, was directed to whole-exome sequencing (WES) of the blood sample to discover a germline variant. In addition, the identified causative variant was confirmed and segregated in other and available unaffected family members. Results: The novel germline heterozygous missense variant, c.2105C>A in the ARMC5 gene, was found, and the same germline variant as the proband was confirmed in two affected sisters. This variant was detected in the brother of the proband with an asymptomatic condition and this considered because of incomplete penetrance and age-dependent appearance. The function of the ARMC5 protein would be damaged by the identified variant, according to in silico and computer analyses that followed. Conclusion: The new germline ARMC5 variation (c.2105C>A, (p. Ala702Glu)) was interpreted as a likely pathogenic variant based on ACMG and Sherloc standards. PMAH may be diagnosed early using genetic testing that shows inherited autosomal dominant mutations in the ARMC5 gene. [ABSTRACT FROM AUTHOR]