PDF(Pubmed)
Abstract：
Capping protein regulator and myosin 1 linker 2 (CARMIL2) is necessary for invadopodia formation, cell polarity, lamellipodial assembly, membrane ruffling, acropinocytosis, and collective cell migration. CARMIL2 deficiency is a rare autosomal recessive disease characterized by dysfunction in naïve T-cell activation, proliferation, differentiation, and effector function and insufficient responses in T-cell memory. In this paper, we report a 9-year-old female patient with a novel pathogenic variant in CARMIL2 (c.2063C > G:p.Thr688Arg) who presented with various symptoms of primary immunodeficiencies including recurrent upper and lower respiratory infections, perioral and perineum papules, reddish impetiginized atopic dermatitis, oral ulcer, painful urination and vaginitis, otitis media, and failure to thrive. A missense mutation leading to insufficient CARMIL2 protein expression, reduced absolute T-cell and natural killer cell (NK cell) counts, and marked skewing to the naïve T-cell form was identified and indicated defective maturation of T cells and B cells. Following 1 year of multitargeted treatment with corticosteroids, hydroxychloroquine, mycophenolate mofetil, and thymosin, the patient presented with significant regression in rashes. CD4+ T-cell, CD8+ T-cell, and NK cell counts were significantly improved.
摘要：
封端蛋白调节因子和肌球蛋白1接头2（CARMIL2）是嵌顿足形成所必需的，细胞极性，层状组件，膜起皱，红细胞增多症,和集体细胞迁移。CARMIL2缺乏症是一种罕见的常染色体隐性遗传疾病，其特征是幼稚T细胞活化功能障碍，扩散,分化,以及效应子功能和T细胞记忆中的反应不足。在本文中,我们报告了一名9岁的女性患者，该患者在CARMIL2中出现了一种新的致病变异（c.2063C>G：p。Thr688Arg）表现为原发性免疫缺陷的各种症状，包括复发性上呼吸道和下呼吸道感染，口周和会阴丘疹，带红色的阻抗化特应性皮炎，口腔溃疡,排尿疼痛和阴道炎，中耳炎,未能茁壮成长。错义突变导致CARMIL2蛋白表达不足，减少绝对T细胞和自然杀伤细胞（NK细胞）计数，和显著的向初始T细胞形式的偏斜被鉴定并指示T细胞和B细胞的有缺陷的成熟。在使用皮质类固醇的多目标治疗1年后，羟氯喹,霉酚酸酯，和胸腺素,患者出现皮疹明显消退。CD4+T细胞，CD8+T细胞，NK细胞计数显著提高。
