1. NOTCH1: Review of its role in lymphatic development and study of seven families with rare pathogenic variants.
- Author
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Michelini S, Ricci M, Serrani R, Barati S, Kenanoglu S, Veselenyiova D, Kurti D, Baglivo M, Basha SH, Priya S, Dautaj A, Dundar M, Krajcovic J, and Bertelli M
- Subjects
- Adolescent, Adult, Aged, Child, Female, Humans, Lymphatic System abnormalities, Lymphedema pathology, Male, Middle Aged, Mutation, Missense, Pedigree, Lymphedema genetics, Receptor, Notch1 genetics
- 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., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
- Published
- 2021
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