CLN5 in heterozygosis may protect against the development of tumors in a VHL patient | Orphanet Journal of Rare Diseases | Full Text

CLN5 in heterozygosis may protect against the development of tumors in a VHL patient | Orphanet Journal of Rare Diseases | Full Text

CLN5 in heterozygosis may protect against the development of tumors in a VHL patient

• Isabel de Rojas-P, 
• Virginia Albiñana, 
• Lucía Recio-Poveda, 
• Amanda Rodriguez-Rufián, 
• Ángel M. Cuesta & 
• Luisa-María Botella 

Orphanet Journal of Rare Diseases volume 15, Article number: 132 (2020) Cite this article

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Abstract

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.