NOTCH1: Review of its role in lymphatic development and study of seven families with rare pathogenic variants
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...
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doaj-9f163611b0e648e7a378d9fd3ad70f832021-03-16T19:33:44ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-01-0191n/an/a10.1002/mgg3.1529NOTCH1: Review of its role in lymphatic development and study of seven families with rare pathogenic variantsSandro Michelini0Maurizio Ricci1Roberta Serrani2Shila Barati3Sercan Kenanoglu4Dominika Veselenyiova5Danjela Kurti6Mirko Baglivo7Syed Hussain Basha8Sasi Priya9Astrit Dautaj10Munis Dundar11Juraj Krajcovic12Matteo Bertelli13Department of Vascular Rehabilitation San Giovanni Battista Hospital Rome ItalyDivision of Rehabilitation Medicine Azienda Ospedaliero‐UniversitariaOspedali Riuniti di Ancona Ancona ItalyDivision of Rehabilitation Medicine Azienda Ospedaliero‐UniversitariaOspedali Riuniti di Ancona Ancona ItalyMAGI EUREGIO Bolzano ItalyMAGI EUREGIO Bolzano ItalyMAGI EUREGIO Bolzano ItalyMAGI EUREGIO Bolzano ItalyMAGI EUREGIO Bolzano ItalyInnovative Informatica Technologies Hyderabad IndiaInnovative Informatica Technologies Hyderabad IndiaMAGI‐Balkans Tirana AlbaniaDepartment of Medical Genetics Faculty of Medicine Erciyes University Kayseri TurkeyDepartment of Biology Faculty of Natural Sciences University of Ss. Cyril and Methodius in Trnava Trnava SlovakiaMAGI EUREGIO Bolzano ItalyAbstract 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.https://doi.org/10.1002/mgg3.1529genetic diagnosislymphedemaNext Generation Sequencing (NGS)NOTCH1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sandro Michelini Maurizio Ricci Roberta Serrani Shila Barati Sercan Kenanoglu Dominika Veselenyiova Danjela Kurti Mirko Baglivo Syed Hussain Basha Sasi Priya Astrit Dautaj Munis Dundar Juraj Krajcovic Matteo Bertelli |
spellingShingle |
Sandro Michelini Maurizio Ricci Roberta Serrani Shila Barati Sercan Kenanoglu Dominika Veselenyiova Danjela Kurti Mirko Baglivo Syed Hussain Basha Sasi Priya Astrit Dautaj Munis Dundar Juraj Krajcovic Matteo Bertelli NOTCH1: Review of its role in lymphatic development and study of seven families with rare pathogenic variants Molecular Genetics & Genomic Medicine genetic diagnosis lymphedema Next Generation Sequencing (NGS) NOTCH1 |
author_facet |
Sandro Michelini Maurizio Ricci Roberta Serrani Shila Barati Sercan Kenanoglu Dominika Veselenyiova Danjela Kurti Mirko Baglivo Syed Hussain Basha Sasi Priya Astrit Dautaj Munis Dundar Juraj Krajcovic Matteo Bertelli |
author_sort |
Sandro Michelini |
title |
NOTCH1: Review of its role in lymphatic development and study of seven families with rare pathogenic variants |
title_short |
NOTCH1: Review of its role in lymphatic development and study of seven families with rare pathogenic variants |
title_full |
NOTCH1: Review of its role in lymphatic development and study of seven families with rare pathogenic variants |
title_fullStr |
NOTCH1: Review of its role in lymphatic development and study of seven families with rare pathogenic variants |
title_full_unstemmed |
NOTCH1: Review of its role in lymphatic development and study of seven families with rare pathogenic variants |
title_sort |
notch1: review of its role in lymphatic development and study of seven families with rare pathogenic variants |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2021-01-01 |
description |
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. |
topic |
genetic diagnosis lymphedema Next Generation Sequencing (NGS) NOTCH1 |
url |
https://doi.org/10.1002/mgg3.1529 |
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