Journal article

Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations

Julie Soblet, Jaakko Kangas, Marjut Natynki, Antonella Mendola, Raphael Helaers, Melanie Uebelhoer, Mika Kaakinen, Maria Cordisco, Anne Dompmartin, Odile Enjolras, Simon Holden, Alan D Irvine, Loshan Kangesu, Christine Leaute-Labreze, Agustina Lanoel, Zerina Lokmic, Saskia Maas, Maeve A McAleer, Anthony Penington, Paul Rieu Show all

Journal of Investigative Dermatology | ELSEVIER SCIENCE INC | Published : 2017

Abstract

Blue rubber bleb nevus syndrome (Bean syndrome) is a rare, severe disorder of unknown cause, characterized by numerous cutaneous and internal venous malformations; gastrointestinal lesions are pathognomonic. We discovered somatic mutations in TEK, the gene encoding TIE2, in 15 of 17 individuals with blue rubber bleb nevus syndrome. Somatic mutations were also identified in five of six individuals with sporadically occurring multifocal venous malformations. In contrast to common unifocal venous malformation, which is most often caused by the somatic L914F TIE2 mutation, multifocal forms are predominantly caused by double (cis) mutations, that is, two somatic mutations on the same allele of th..

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Grants

Awarded by Belgian Science Policy Office Interuniversity Attraction Poles (BELSPO-IAP)


Awarded by National Institute of Health


Awarded by Fonds de la Recherche Scientifique-FNRS


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Funding Acknowledgements

We are grateful to all the patients and their family members. We thank Liliana Niculescu for secretarial help, and Jaana Traskelin and Riitta Jokela for their excellent technical assistance. These studies were partially supported by funding from the Belgian Science Policy Office Interuniversity Attraction Poles (BELSPO-IAP) program through the project IAP P7/43-BeMGI; the National Institute of Health, Program Project P01 AR048564; the Fonds de la Recherche Scientifique-FNRS (PDR T.0026.14), the Fonds de la Recherche Scientifique-FNRS for the FRFS-WELBIO-CR-2015A-10. We also acknowledge the support of la Communaute francaise de Wallonie-Bruxelles, la Lotterie nationale, Belgium, and the Stuart and Jane Weitzman Family Fund, Children's Hospital Boston. JS was supported by a Pierre M. fellowship. NL is a Chercheur Qualifie of the Fonds de la Recherche Scientifique-FNRS. We also thank the Genomics Platform of Universite catholique de Louvain for access to the next-generation sequencing data analysis.