Sandro Michelini1, Maurizio Ricci2, Roberta Serrani2, Shila Barati3, Sercan Kenanoglu3,4, Dominika Veselenyiova3,5, Danjela Kurti3,6, Mirko Baglivo3, Syed Hussain Basha7, Sasi Priya7, Astrit Dautaj6,8, Munis Dundar4, Juraj Krajcovic5, Matteo Bertelli3,8,9. 1. Department of Vascular Rehabilitation, San Giovanni Battista Hospital, Rome, Italy. 2. Division of Rehabilitation Medicine, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Ancona, Italy. 3. MAGI EUREGIO, Bolzano, Italy. 4. Department of Medical Genetics, Faculty of Medicine, Erciyes University, Kayseri, Turkey. 5. Department of Biology, Faculty of Natural Sciences, University of Ss. Cyril and Methodius in Trnava, Trnava, Slovakia. 6. MAGI-Balkans, Tirana, Albania. 7. Innovative Informatica Technologies, Hyderabad, India. 8. EBTNA-LAB, Rovereto, Italy. 9. MAGI'S LAB, Rovereto, Italy.
Abstract
BACKGROUND: We developed a Next-Generation-Sequencing (NGS) protocol to screen the most frequent genetic variants related to lymphedema and a group of candidate genes. The aim of the study was to find the genetic cause of lymphedema in the analyzed patients. METHODS: We sequenced a cohort of 246 Italian patients with lymphatic malformations. In the first step, we analyzed genes known to be linked to lymphedema: 235 out of 246 patients tested negative for the most frequent variants and underwent testing for variants in a group of candidate genes, including the NOTCH1 gene, selected from the database of mouse models. We also performed in silico analysis to observe molecular interactions between the wild-type and the variant amino acids and other protein residues. RESULTS: Seven out of 235 probands, five with sporadic and two with familial lymphedema, were found to carry rare missense variants in the NOTCH1 gene. CONCLUSIONS: Our results propose that NOTCH1 could be a novel candidate for genetic predisposition to lymphedema.
BACKGROUND: We developed a Next-Generation-Sequencing (NGS) protocol to screen the most frequent genetic variants related to lymphedema and a group of candidate genes. The aim of the study was to find the genetic cause of lymphedema in the analyzed patients. METHODS: We sequenced a cohort of 246 Italian patients with lymphatic malformations. In the first step, we analyzed genes known to be linked to lymphedema: 235 out of 246 patients tested negative for the most frequent variants and underwent testing for variants in a group of candidate genes, including the NOTCH1 gene, selected from the database of mouse models. We also performed in silico analysis to observe molecular interactions between the wild-type and the variant amino acids and other protein residues. RESULTS: Seven out of 235 probands, five with sporadic and two with familial lymphedema, were found to carry rare missense variants in the NOTCH1 gene. CONCLUSIONS: Our results propose that NOTCH1 could be a novel candidate for genetic predisposition to lymphedema.
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