Von Hippel-Lindau (VHL) syndrome is an autosomal dominantly inherited disorder that predisposes to multiple neoplasms. Patients may develop hemangioblastomas of the central nervous system and retina, multiple cysts in the pancreas and kidneys, renal carcinoma, and pheochromocytomas, among other lesions. This disease is caused by germline genetic variants in the VHL gene. The regulation of the alpha subunit of hypoxia-inducible factor-1 is the key tumor suppressor function of the VHL protein. To date, more than seven hundred variants have been reported in VHL gene. This study aimed to investigate the molecular etiology of VHL syndrome in Cuban patients. DNA samples from twenty-two individuals were analyzed by Sanger sequencing or enzymatic restriction. The analysis identified four novel pathogenic variants for the Cuban population: c.463 + 2T > C, C162W, R167W, and S183X, in addition to D121G and R161X, previously described in another work. The diagnosis was confirmed in seven patients with clinical manifestations and family history. Two at-risk family members without clinical signs were positive for presymptomatic diagnosis. The spectrum of germinal point mutations of VHL gene in Cuban patients was updated. The presence of genetic variants was ruled out in eight asymptomatic relatives, which is a psychological relief for these individuals. The results allow for offering other at-risk relatives the presymptomatic diagnosis and the possibility of receiving genetic counseling.

中文翻译：

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古巴患者 Von Hippel-Lindau 肿瘤抑制基因的种系变异

Von Hippel-Lindau (VHL) 综合征是一种常染色体显性遗传性疾病，易患多种肿瘤。患者可能会出现中枢神经系统和视网膜的血管母细胞瘤、胰腺和肾脏的多发性囊肿、肾癌和嗜铬细胞瘤等病变。这种疾病是由 VHL 基因的种系遗传变异引起的。缺氧诱导因子-1 α 亚基的调节是 VHL 蛋白的关键抑癌功能。迄今为止，VHL基因已报道了七百多种变异。本研究旨在探讨古巴患者 VHL 综合征的分子病因学。通过桑格测序或酶切技术对 22 名个体的 DNA 样本进行了分析。该分析确定了古巴人群的四种新致病变异：c.463 + 2T > C、C162W、R167W 和 S183X，以及先前在另一项工作中描述的 D121G 和 R161X。7 名具有临床表现和家族史的患者确诊。两名没有临床症状的高危家庭成员症状前诊断呈阳性。更新了古巴患者VHL基因生发点突变谱。八名无症状亲属的基因变异被排除，这对这些人来说是一种心理安慰。研究结果可以为其他高危亲属提供症状前诊断和接受遗传咨询的可能性。