Investigation on the role of biallelic variants in VEGF-C found in a patient affected by Milroy-like lymphedema
| Autor: | Sylvain Mukenge, Matteo Bertelli, Andrea Brendolan, Elisa Lenti, Michael Jeltsch, Luca Aldrighetti, Sawan Kumar Jha, Daniela Negrini, Elena Manara, Veli-Matti Leppänen, Marco Catena |
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| Přispěvatelé: | CAN-PRO - Translational Cancer Medicine Program, Michael Jeltsch / Principal Investigator, Research Programs Unit, University of Helsinki, Kari Alitalo / Principal Investigator, Helsinki One Health (HOH), INDIVIDRUG - Individualized Drug Therapy, Mukenge, S., Jha, S. K., Catena, M., Manara, E., Leppanen, V. -M., Lenti, E., Negrini, D., Bertelli, M., Brendolan, A., Jeltsch, M., Aldrighetti, L. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Proband Male lymphatic system Milroy disease mutation primary lymphedema VEGF-C VEGF‐C Vascular Endothelial Growth Factor C Disease 030105 genetics & heredity medicine.disease_cause GROWTH FACTOR-C Lymphedema Child Genetics (clinical) Genetics Mutation medicine.diagnostic_test 1184 Genetics developmental biology physiology Middle Aged Pedigree Phenotype Original Article Female LYMPHANGIOGENESIS Adult lcsh:QH426-470 Mutation Missense MECHANISMS 03 medical and health sciences medicine Humans Primary lymphedema Molecular Biology Alleles Genetic testing business.industry Original Articles medicine.disease FLT4 lcsh:Genetics 030104 developmental biology Etiology 3111 Biomedicine business |
| Zdroj: | Molecular Genetics & Genomic Medicine Molecular Genetics & Genomic Medicine, Vol 8, Iss 9, Pp n/a-n/a (2020) |
| Popis: | Background Milroy‐like disease is the diagnostic definition used for patients with phenotypes that resemble classic Milroy disease (MD) but are negative to genetic testing for FLT4. In this study, we aimed at performing a genetic characterization and biochemical analysis of VEGF‐C variations found in a female proband born with congenital edema consistent with Milroy‐like disease. Methods The proband underwent next‐generation sequencing‐based genetic testing for a panel of genes associated with known forms of hereditary lymphedema. Segregation analysis was performed on family members by direct sequencing. In vitro studies were performed to evaluate the role of a novel identified variant. Results Two VEGF‐C variations were found in the proband, a novel p.(Ser65Arg) and a pathogenic c.148‐3_148‐2delCA, of paternal and maternal origin, respectively. Functional characterization of the p.(Ser65Arg) variation in vitro showed alterations in VEGF‐C processing. Conclusions Our findings reveal an interesting case in which biallelic variants in VEGF‐C are found in a patient with Milroy‐like lymphedema. These data expand our understanding of the etiology of congenital Milroy‐like lymphedema. A genetic and biochemical analysis of VEGF‐C variations were performed on a female proband affected by primary lymphedema of the right lower limb and on her entire family. Biallelic variants of VEGF‐C variations were found in the proband: a novel p.(Ser65Arg) and a pathogenic c.148‐3_148‐2del, of paternal and maternal origin, respectively. Clinical examination of the family by lymphoscintigraphy as well as biochemical analysis show that both variants are required to the development of the proband Milroy‐like lymphedema. |
| Databáze: | OpenAIRE |
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