TY - JOUR
T1 - Mutations in the ARAP3 Gene in Three Families with Primary Lymphedema Negative for Mutations in Known Lymphedema-Associated Genes
AU - Ricci, Maurizio
AU - Compagna, Rita
AU - Amato, Bruno
AU - Kenanoglu, Sercan
AU - Veselenyiova, Dominika
AU - Kurti, Danjela
AU - Baglivo, Mirko
AU - Basha, Syed Hussain
AU - Serrani, Roberta
AU - Miggiano, Giacinto Abele Donato
AU - Aquilanti, Barbara
AU - Matera, Giuseppina
AU - Marceddu, Giuseppe
AU - Velluti, Valeria
AU - Gagliardi, Lucilla
AU - Dundar, Munis
AU - Krajcovic, Juraj
AU - Bertelli, Matteo
N1 - Publisher Copyright:
© 2020 Maurizio Ricci et al.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background. ARAP3 is a small GTPase-activating protein regulator, which has important functions in lymphatic vessel organogenesis and modulation of cell adhesion and migration. Mutations in the ARAP3 gene are associated with impaired lymphatic vessel formation. Objective. The aim of our study was to determine the genotypes of lymphedema patients in relation to variants in the ARAP3 gene in order to explore its role in the development of lymphedema. Methods and Results. We applied next-generation sequencing to DNA samples of a cohort of 246 Italian patients with lymphatic malformations. When we tested probands for known lymphedema genes, 235 out of 246 were negative. Retrospectively, we tested the DNA of these 235 patients for new candidate lymphedema-associated genes, including ARAP3. Three out of 235 probands proved to carry rare missense heterozygous variants in ARAP3. In the case of two families, other family members were also tested and proved negative for the ARAP3 variant, besides being unaffected by lymphedema. According to in silico analysis, alterations due to these variants have a significant impact on the overall structure and stability of the resulting proteins. Conclusions. Based on our results, we propose that variants in ARAP3 could be included in genetic testing for lymphedema.
AB - Background. ARAP3 is a small GTPase-activating protein regulator, which has important functions in lymphatic vessel organogenesis and modulation of cell adhesion and migration. Mutations in the ARAP3 gene are associated with impaired lymphatic vessel formation. Objective. The aim of our study was to determine the genotypes of lymphedema patients in relation to variants in the ARAP3 gene in order to explore its role in the development of lymphedema. Methods and Results. We applied next-generation sequencing to DNA samples of a cohort of 246 Italian patients with lymphatic malformations. When we tested probands for known lymphedema genes, 235 out of 246 were negative. Retrospectively, we tested the DNA of these 235 patients for new candidate lymphedema-associated genes, including ARAP3. Three out of 235 probands proved to carry rare missense heterozygous variants in ARAP3. In the case of two families, other family members were also tested and proved negative for the ARAP3 variant, besides being unaffected by lymphedema. According to in silico analysis, alterations due to these variants have a significant impact on the overall structure and stability of the resulting proteins. Conclusions. Based on our results, we propose that variants in ARAP3 could be included in genetic testing for lymphedema.
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U2 - 10.1155/2020/3781791
DO - 10.1155/2020/3781791
M3 - Article
AN - SCOPUS:85091460451
VL - 2020
JO - International Journal of Genomics
JF - International Journal of Genomics
SN - 2314-436X
M1 - 3781791
ER -