Pathogenic variants in the <i>IFT140</i> gene and an intriguing clinical presentation in two pediatric patients. Cases report and review of literature

The <i>IFT140</i> gene is one of many genes involved in the synthesis of proteins needed for cilium function. Ciliopathies are a group of disorders associated with the dysfunction of ciliary structures and express as an individual organ system disease as well as multisystem disorders. Dysfunctional cilia typically manifest as pleiotropic clinical features, reflecting their widespread distribution and varied functionality. We present two cases: Case 1, a male with two pathological variations in <i>IFT140</i> gene, a compound heterozygote, with kidney failure, retinal dystrophy, cardiomyopathy, and situs inversus and Case 2, a female with an <i>IFT140</i> pathogenic homozygous variant, presented with nephrotic range proteinuria, retinitis pigmentosa, and pseudotumor cerebri. As cilia dysfunction is known to cause pleiotropic clinical features due to the presence of cilia in different organs in the body, the clinical picture of the <i>IFT140</i> mutation is also very heterogeneous. Our cases reveal unprecedented manifestations — LVNC, situs inversus, and pseudotumor cerebri — not previously documented in <i>IFT140</i> mutation. These findings underscore the importance of genetic screening in ciliopathies.IFT140基因（IFT140）是参与纤毛功能所需蛋白质合成过程的众多基因之一。纤毛病（Ciliopathies）是一组与纤毛结构功能异常相关的疾病，既可表现为单一器官系统疾病，也可表现为多系统疾病。纤毛功能异常通常呈现多效性临床特征，这与其在体内广泛分布且功能多样的特点相契合。本研究报告两例病例：病例1为一名IFT140基因存在两处病理性变异的复合杂合子男性患者，临床表现为肾衰竭、视网膜营养不良、心肌病及内脏反位；病例2为一名IFT140基因携带致病性纯合变异的女性患者，表现为肾病范围蛋白尿、色素性视网膜炎及假脑瘤综合征。由于纤毛广泛分布于人体不同器官，纤毛功能异常可引发多效性临床特征，因此IFT140基因突变的临床表现具有高度异质性。本研究报道的病例展现了IFT140基因突变中此前未被文献记录的全新临床表现——左心室非致密化心肌病（LVNC）、内脏反位及假脑瘤综合征。上述研究结果凸显了纤毛病患者开展基因筛查的重要性。