Molecular genetics & genomic medicine · 2020
Two rare PROX1 variants in patients with lymphedema.
Клинический случайСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Ricci Maurizio, Amato Bruno, Barati Shila, Compagna Rita, Veselenyiova Dominika, Kenanoglu Sercan, Stuppia Liborio, Beccari Tommaso, Baglivo Mirko, Kurti Danjela, Krajcovic Juraj, Serrani Roberta, Dundar Munis, Basha Syed H, Chiurazzi Pietro, Bertelli Matteo
Аннотация
BACKGROUND: The PROX1 gene is specifically expressed in a subpopulation of endothelial cells that, by budding and sprouting, give rise to the lymphatic system. It also plays a critical role in neurogenesis and during development of many organs, such as the eye lens, liver, and pancreas.
METHODS: We used next-generation sequencing (NGS) to sequence the DNA of a cohort of 246 Italian patients with lymphatic malformations. We first investigated 29 known disease-causing genes: 235 of 246 patients tested negative and were then retested for a group of candidate genes, including PROX1, selected from a database of mouse models. The aim of the study was to define these patients' genotypes and explore the role of the candidate gene PROX1 in lymphedema.
RESULTS: Two of 235 probands were found to carry rare heterozygous missense variants in PROX1. In silico analysis of these variants-p.(Leu590His) and p.(Gly106Asp)-indicates that the overall protein structure was altered by changes in interactions between nearby residues, leading to functional protein defects.
CONCLUSIONS: Our results suggest that PROX1 is a new candidate gene for predisposition to lymphedema.
METHODS: We used next-generation sequencing (NGS) to sequence the DNA of a cohort of 246 Italian patients with lymphatic malformations. We first investigated 29 known disease-causing genes: 235 of 246 patients tested negative and were then retested for a group of candidate genes, including PROX1, selected from a database of mouse models. The aim of the study was to define these patients' genotypes and explore the role of the candidate gene PROX1 in lymphedema.
RESULTS: Two of 235 probands were found to carry rare heterozygous missense variants in PROX1. In silico analysis of these variants-p.(Leu590His) and p.(Gly106Asp)-indicates that the overall protein structure was altered by changes in interactions between nearby residues, leading to functional protein defects.
CONCLUSIONS: Our results suggest that PROX1 is a new candidate gene for predisposition to lymphedema.