Open AccessNOTCH1 : Review of its role in lymphatic development and study of seven families with rare pathogenic variants
Author(s) -
Michelini Sandro,
Ricci Maurizio,
Serrani Roberta,
Barati Shila,
Kenanoglu Sercan,
Veselenyiova Dominika,
Kurti Danjela,
Baglivo Mirko,
Basha Syed Hussain,
Priya Sasi,
Dautaj Astrit,
Dundar Munis,
Krajcovic Juraj,
Bertelli Matteo
Publication year - 2021
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1529
Subject(s) - lymphedema , candidate gene , proband , missense mutation , in silico , genetics , gene , biology , medicine , bioinformatics , phenotype , mutation , cancer , breast cancer
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.