Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), group U707, 28040, Madrid, Spain.
Orphanet J Rare Dis. 2020 Jun 2;15(1):132. doi: 10.1186/s13023-020-01410-y.
Von Hippel-Lindau syndrome (VHL) is a rare disease of dominant inheritance that increases susceptibility to tumor development, with a complete penetrance at the age of 60. In this report, we present the unprecedented case of a VHL carrier who remains healthy at 72. Under the course of this study, it was discovered that this patient carries a mutation for a second rare disease, Neuronal Ceroid Lipofuscinosis (NCL or CNL). We hypothesize that the CLN mutation she carries offers a protective effect, preventing tumor development in the cells potentially suffering a VHL second hit mutation. To test this hypothesis, we ran a series of molecular experiments and confirmed that cell viability of primary endothelial cells decreases upon CLN5 silencing. Our results further elucidate the cell biology implications of two rare diseases interacting.
希佩尔-林道综合征（VHL）是一种罕见的显性遗传疾病，增加了肿瘤发展的易感性，60 岁时完全外显。在本报告中，我们首次报道了一例 VHL 携带者，他在 72 岁时仍然健康。在这项研究的过程中，发现该患者携带第二种罕见疾病神经元蜡样脂褐质沉积症（NCL 或 CNL）的突变。我们假设她携带的 CLN 突变提供了一种保护作用，防止潜在遭受 VHL 二次打击突变的细胞发生肿瘤。为了验证这一假设，我们进行了一系列分子实验，证实了 CLN5 沉默后原代内皮细胞的活力下降。我们的结果进一步阐明了两种罕见疾病相互作用的细胞生物学意义。
