Open AccessRARE PECAM1 VARIANTS IN THREE FAMILIES WITH LYMPHEDEMA
Author(s) -
Sandro Michelini,
Bruno Amato,
Sercan Kenanoğlu,
Dominika Vešelényiová,
Astrit Dautaj,
Danjela Kurti,
Mirko Baglivo,
Munis Dündar,
Juraj Krajčovič,
GAD Miggiano,
Barbara Aquilanti,
Giuseppina Matera,
Valeria Velluti,
Lucilla Gagliardi,
SH Basha,
Matteo Bertelli
Publication year - 2021
Publication title -
lymphology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.21
H-Index - 46
eISSN - 2522-7963
pISSN - 0024-7766
DOI - 10.2458/lymph.4666
Subject(s) - lymphedema , proband , lymphatic system , missense mutation , immunoglobulin superfamily , medicine , biology , pathology , genetics , gene , phenotype , mutation , cancer , breast cancer
PECAM1 is a member of the immunoglobulin superfamily and is expressed in monocytes, neutrophils, macrophages and other types of immune cells as well as in endothelial cells. PECAM1 function is crucial for the development and maturation of B lymphocytes. The aim of this study was to link rare PECAM1 variants found in lymphedema patients with the development of lymphatic system malformations. Using NGS, we previously tested 246 Italian lymphedema patients for variants in 29 lymphedema-associated genes and obtained 235 negative results. We then tested these patients for variants in the PECAM1 gene. We found three probands with rare variants in PECAM1. All variants were heterozygous missense variants. In Family 1, the unaffected mother and brother of the proband were found to carry the same variant as the proband. Lymphoscintigraphy was performed to determine possible lymphatic malformations and showed that in both cases a bilateral slight reduction in the speed and lymphatic clearance of the lower limbs. PECAM1 function is important for lymphatic vasculature formation. We found variants in PECAM1 that may be associated with susceptibility to lymphedema.