Alomari Omar, Ertan Sinem Nur, Mokresh Muhammed Edib, Yazicilar Elif, Pourali Maryam, Akyokus Fatma Esra, Sager Safiye Gunes, Cag Yakup
Hamidiye International School of Medicine, University of Health Sciences, Istanbul, Turkey.
Clinics of Pediatric Neurology, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey.
Am J Med Genet A. 2025 Jan;197(1):e63855. doi: 10.1002/ajmg.a.63855. Epub 2024 Aug 21.
FCH domain only 1 (FCHO1) is a key player in clathrin-mediated endocytosis, vital for various cellular processes, including immune regulation and cancer progression. However, the clinical implications of FCHO1 mutations, particularly in combined immunodeficiency, remain unclear. This systematic review aims to provide an objective analysis of the molecular genetics, clinical manifestations, and potential therapeutic targets associated with FCHO1 mutations. A systematic search following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted across electronic databases up to March 25, 2024, to identify studies investigating the relationship between FCHO1 and different clinical manifestations. Eligibility criteria were applied to screen studies, and data extraction included study characteristics, reported symptoms, genetic variants, and primary outcomes. In silico analyses were performed to assess protein-protein interactions and gene expression patterns. Five studies were included, offering insights into the molecular genetics, T-cell deficiency mechanisms, clinical manifestations, and potential therapeutic targets associated with FCHO1 mutations. Molecular analyses identified specific mutations disrupting FCHO1 function, leading to impaired T-cell proliferation, cytokine production, and susceptibility to infections. Clinically, patients exhibited recurrent infections, lymphopenia, and malignancies, with allogeneic hematopoietic stem cell transplantation emerging as a therapeutic option. In silico analyses revealed potential interactions and co-expression between FCHO1 and genes involved in cancer progression and immune signaling pathways. This systematic review objectively elucidates the multifaceted role of FCHO1 in immune regulation and disease pathogenesis. Understanding the molecular mechanisms underlying FCHO1 mutations and their impact on disease manifestations is crucial for guiding clinical management and developing targeted therapeutic strategies.
仅含FCH结构域蛋白1（FCHO1）是网格蛋白介导的内吞作用中的关键因子，对包括免疫调节和癌症进展在内的各种细胞过程至关重要。然而，FCHO1突变的临床意义，尤其是在联合免疫缺陷中的临床意义仍不明确。本系统评价旨在对与FCHO1突变相关的分子遗传学、临床表现及潜在治疗靶点进行客观分析。按照系统评价和Meta分析的首选报告项目（PRISMA）指南，截至2024年3月25日在电子数据库中进行了系统检索，以识别研究FCHO1与不同临床表现之间关系的研究。应用纳入标准筛选研究，数据提取包括研究特征、报告的症状、基因变异和主要结局。进行了计算机模拟分析以评估蛋白质-蛋白质相互作用和基因表达模式。纳入了五项研究，这些研究对与FCHO1突变相关的分子遗传学、T细胞缺陷机制、临床表现及潜在治疗靶点提供了见解。分子分析确定了破坏FCHO1功能的特定突变，导致T细胞增殖受损、细胞因子产生受损以及对感染的易感性增加。临床上，患者表现出反复感染、淋巴细胞减少和恶性肿瘤，异基因造血干细胞移植成为一种治疗选择。计算机模拟分析揭示了FCHO1与参与癌症进展和免疫信号通路的基因之间的潜在相互作用和共表达。本系统评价客观地阐明了FCHO1在免疫调节和疾病发病机制中的多方面作用。了解FCHO1突变的分子机制及其对疾病表现形式的影响对于指导临床管理和制定靶向治疗策略至关重要。
