Inherited germline mutations in the VHL gene cause predisposition to Von Hippel-Lindau (VHL) disease. Patients exhibit benign and cancerous lesions in multiple tissues, including hemangioblastomas, clear cell renal cell carcinoma, cysts in kidneys and pancreas, and pheochromocytomas. Although pathogenic germline mutations in the VHL gene have been widely described in different populations, only a single mutation was previously reported in a family from mixed Arab-Persian ethnicity. Here, we present five Arab patients with two new and two recurrent germline mutations in the VHL gene. These mutations include three in-frame deletions and a missense mutation. Infrequent in-frame deletions in previously described patients from other populations, as well as the presence of new mutations, suggests a distinct spectrum of VHL gene mutations in Arab patients. While pulmonary manifestation has been described rarely in VHL disease, we have identified two patients with a recurrent p.Phe76del in-frame deletion exhibiting multiple nodules in lungs. We also describe a first-ever in-frame deletion in the VHL gene in a patient with VHL type 2C disease, exhibiting bilateral pheochromocytoma. Overall, the study provides an insight into the genotype-phenotype relationship of VHL disease in Arab patients and provides a comparison with previously described patients from other ethnicities.

VHL基因中遗传的种系突变导致易Hippel-Lindau（VHL）疾病易感。患者在多个组织中表现出良性和癌性病变，包括血管母细胞瘤，透明细胞肾细胞癌，肾脏和胰腺的囊肿以及嗜铬细胞瘤。尽管已在不同人群中广泛描述了VHL基因中的致病性生殖系突变，但以前在阿拉伯和波斯混血的家庭中仅报道了一个突变。在这里，我们介绍了五名阿拉伯患者，他们在VHL中有两个新的和两个复发的种系突变基因。这些突变包括三个框内缺失和错义突变。先前描述的其他人群中的患者很少出现框内缺失，以及新突变的出现，表明阿拉伯患者的VHL基因突变谱范围很广。尽管很少有人在VHL疾病中描述过肺部表现，但我们已经确定了两名复发性p.Phe76del框内缺失并在肺部显示多个结节的患者。我们还将描述VHL中的首次帧内删除VHL 2C型患者的双侧嗜铬细胞瘤基因。总体而言，该研究提供了对阿拉伯患者中VHL疾病的基因型与表型关系的深入了解，并与先前描述的来自其他种族的患者进行了比较。