Özdemiral Cansu, Yaz Ismail, Esenboga Saliha, Nabiyeva Cevik Nadira, Bildik Hacer Neslihan, Kilic Mehmet, Tezcan Ilhan, Cagdas Deniz
Division of Immunology, Department of Pediatrics, Hacettepe University Medical School, Ankara, Türkiye.
İhsan Doğramacı Children's Hospital, Hacettepe University, Ankara, Türkiye.
Clin Exp Immunol. 2025 Jan 21;219(1). doi: 10.1093/cei/uxae097.
F-BAR domain only protein 1 (FCHO1) contributes as a critical component to an essential cellular process, clathrin-mediated endocytosis. Clathrin-mediated endocytosis involves cellular membrane invagination followed by cargo protein recruitment and adaptor protein assembly to form endocytic vesicles and maintains several cellular functions, such as signaling, differentiation, nutrition, absorption, and secretion. We aimed to determine the clinical/immunological findings of FCHO1 deficiency to generate an appropriate medical approach. We present clinical/immunological/genetic findings of two FCHO1 deficiency patients together with recently reported 17 patients. We found two different variants in the patients, one previously defined and one novel homozygous mutation [c.306C > A (p.Tyr102Ter)]. Recurrent sinopulmonary infections occurred in all patients, with viral (63.1%) and fungal (52.6%) infections frequently reported. Lymphopenia and CD4 + T cell lymphopenia are present in 77.7% (14/18) and 100% of patients, respectively. CD8+ T cell number is low in half. Hypogammaglobulinemia and low IgM are present in 83.3% (15/18) and 61.1% (11/18) of patients, respectively. Neurological disorders (Guillian-Barre Syndrome, Moya-Moya disease, encephalitis, and cranial infarction) are common [n = 6 (31.5%)]. Malignancy is present in four (21%) patients, three suffered from diffuse large B cell lymphoma, and one developed Hodgkin lymphoma. Additional clinical and laboratory results from more patients helped to define the characteristics of FCHO1 deficiency. The early application of molecular genetic analysis in CID patients is crucial. Since all transplanted patients were alive, allogeneic hematopoietic stem cell transplantation emerged as a potential curative therapy.
仅含F-BAR结构域蛋白1（FCHO1）是网格蛋白介导的内吞作用这一重要细胞过程的关键组成部分。网格蛋白介导的内吞作用包括细胞膜内陷，随后募集货物蛋白并组装衔接蛋白以形成内吞小泡，并维持多种细胞功能，如信号传导、分化、营养摄取、吸收和分泌。我们旨在确定FCHO1缺乏症的临床/免疫学表现，以制定合适的医疗方案。我们展示了两名FCHO1缺乏症患者以及最近报道的17名患者的临床/免疫学/遗传学表现。我们在患者中发现了两种不同的变异，一种是先前确定的，另一种是新的纯合突变[c.306C>A（p.Tyr102Ter）]。所有患者均反复发生鼻窦肺部感染，常见病毒感染（63.1%）和真菌感染（52.6%）。淋巴细胞减少症和CD4+T细胞淋巴细胞减少症分别出现在77.7%（14/18）和100%的患者中。一半患者的CD8+T细胞数量较低。低丙种球蛋白血症和低IgM分别出现在83.3%（15/18）和61.1%（11/18）的患者中。神经系统疾病（格林-巴利综合征、烟雾病、脑炎和脑梗死）很常见[n = 6（31.5%）]。4名（21%）患者患有恶性肿瘤，3名患有弥漫性大B细胞淋巴瘤，1名患霍奇金淋巴瘤。更多患者的其他临床和实验室结果有助于明确FCHO1缺乏症的特征。对原发性免疫缺陷病患者早期应用分子遗传学分析至关重要。由于所有移植患者均存活，同种异体造血干细胞移植成为一种潜在的治愈性疗法。
