Clinical analysis of ARMC gene alteration

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07334
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Shizuoka Graduate University of Public Health
• Principal Investigator: Usui Takeshi 静岡社会健康医学大学院大学, 社会健康医学研究科, 教授 (20271512)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 原発性マクロ結節性副腎過形成 / ARMC5

Outline of Final Research Achievements

Primary macronodular adrenal hyperplasia (PMAH) is one of the conditions that can cause Cushing's syndrome (CS) or subclinical CS. The ARMC5 gene has been identified as a causative gene for PMAH. This study analyzed the genetic and clinical phenotypes of 34 patients from 32 Japanese families with PMAH. Pathogenic or likely pathogenic ARMC5 variants were identified in 14 of the 32 families. Among these, five families shared the same variant. Two children of the patients also had the variants in asymptomatic or pre-symptomatic states. The ARMC5 variant-positive group had higher baseline cortisol (F) levels compared to the variant-negative group, and an age-dependent increase in F hypersecretion was observed. Pathogenic ARMC5 variants were confirmed in 43% of Japanese PMAH patients.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

高血圧、糖尿病、脂質代謝異常症等の生活習慣病に対する対策は健康長寿社会の実現のためにも重要な課題である。内分泌疾患であるクッシング病やその軽症型であるサブクリニカルクッシング症候群は時として上記の疾患の背後に潜んでいることがある。原発性マクロ結節性副腎過形成（PMAH）はそのような病態を呈する稀な病態と考えられていたがその多くが遺伝性疾患であり必ずしも診断されていない可能性があることは重要な所見である。