Mutations in the ARAP3 Gene in Three Families with Primary Lymphedema Negative for Mutations in Known Lymphedema-Associated Genes
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...
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| Format: | Article |
| Language: | English |
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Hindawi Limited
2020-01-01
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| Series: | International Journal of Genomics |
| Online Access: | http://dx.doi.org/10.1155/2020/3781791 |
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doaj-4d5a6d9410cc418483d70286d9dcd1a22020-11-25T03:26:08ZengHindawi LimitedInternational Journal of Genomics2314-436X2314-43782020-01-01202010.1155/2020/37817913781791Mutations in the ARAP3 Gene in Three Families with Primary Lymphedema Negative for Mutations in Known Lymphedema-Associated GenesMaurizio Ricci0Rita Compagna1Bruno Amato2Sercan Kenanoglu3Dominika Veselenyiova4Danjela Kurti5Mirko Baglivo6Syed Hussain Basha7Roberta Serrani8Giacinto Abele Donato Miggiano9Barbara Aquilanti10Giuseppina Matera11Giuseppe Marceddu12Valeria Velluti13Lucilla Gagliardi14Munis Dundar15Juraj Krajcovic16Matteo Bertelli17Division of Rehabilitation Medicine, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, ItalyDepartment of Public Health, University of Naples Federico II, Naples, ItalyDepartment of General and Geriatric Surgery, University of Naples “Federico II”, Naples, ItalyDepartment of Medical Genetics, Faculty of Medicine, Erciyes University, Kayseri, TurkeyMAGI Euregio, Bolzano, ItalyMAGI Euregio, Bolzano, ItalyMAGI Euregio, Bolzano, ItalyInnovative Informatica Technologies, Hyderabad, IndiaDivision of Rehabilitation Medicine, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, ItalyUOC Nutrizione Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, ItalyUOC Nutrizione Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, ItalyUOC Nutrizione Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, ItalyMAGI Euregio, Bolzano, ItalyUOC Nutrizione Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, ItalyUOC Nutrizione Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, ItalyDepartment 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, ItalyBackground. 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.http://dx.doi.org/10.1155/2020/3781791 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Maurizio Ricci Rita Compagna Bruno Amato Sercan Kenanoglu Dominika Veselenyiova Danjela Kurti Mirko Baglivo Syed Hussain Basha Roberta Serrani Giacinto Abele Donato Miggiano Barbara Aquilanti Giuseppina Matera Giuseppe Marceddu Valeria Velluti Lucilla Gagliardi Munis Dundar Juraj Krajcovic Matteo Bertelli |
| spellingShingle |
Maurizio Ricci Rita Compagna Bruno Amato Sercan Kenanoglu Dominika Veselenyiova Danjela Kurti Mirko Baglivo Syed Hussain Basha Roberta Serrani Giacinto Abele Donato Miggiano Barbara Aquilanti Giuseppina Matera Giuseppe Marceddu Valeria Velluti Lucilla Gagliardi Munis Dundar Juraj Krajcovic Matteo Bertelli Mutations in the ARAP3 Gene in Three Families with Primary Lymphedema Negative for Mutations in Known Lymphedema-Associated Genes International Journal of Genomics |
| author_facet |
Maurizio Ricci Rita Compagna Bruno Amato Sercan Kenanoglu Dominika Veselenyiova Danjela Kurti Mirko Baglivo Syed Hussain Basha Roberta Serrani Giacinto Abele Donato Miggiano Barbara Aquilanti Giuseppina Matera Giuseppe Marceddu Valeria Velluti Lucilla Gagliardi Munis Dundar Juraj Krajcovic Matteo Bertelli |
| author_sort |
Maurizio Ricci |
| title |
Mutations in the ARAP3 Gene in Three Families with Primary Lymphedema Negative for Mutations in Known Lymphedema-Associated Genes |
| title_short |
Mutations in the ARAP3 Gene in Three Families with Primary Lymphedema Negative for Mutations in Known Lymphedema-Associated Genes |
| title_full |
Mutations in the ARAP3 Gene in Three Families with Primary Lymphedema Negative for Mutations in Known Lymphedema-Associated Genes |
| title_fullStr |
Mutations in the ARAP3 Gene in Three Families with Primary Lymphedema Negative for Mutations in Known Lymphedema-Associated Genes |
| title_full_unstemmed |
Mutations in the ARAP3 Gene in Three Families with Primary Lymphedema Negative for Mutations in Known Lymphedema-Associated Genes |
| title_sort |
mutations in the arap3 gene in three families with primary lymphedema negative for mutations in known lymphedema-associated genes |
| publisher |
Hindawi Limited |
| series |
International Journal of Genomics |
| issn |
2314-436X 2314-4378 |
| publishDate |
2020-01-01 |
| description |
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. |
| url |
http://dx.doi.org/10.1155/2020/3781791 |
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