Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2014 Hydrops, fetal pleural efusions and chylothorax in three patients with CBL mutations Bülow, Luzie ; Lissewski, Christina ; Bressel, Rainer ; Rauch, Anita ; Stark, Zornitza ; Zenker, Martin ; Bartsch, Oliver Abstract: Fetal hydrops, fetal pleural efusions, hydrothorax, and chylothorax, may be associated with various genetic disorders, in particular with the Noonan, cardio-facio-cutaneous and Costello syndromes. These syndromes, collectively called RASopathies, are caused by mutations in the RAS/MAPK pathway, which is known to play a major role in lymphangiogenesis. Recently, germline mutations in the Casitas B-cell lymphoma (CBL) gene were reported in 25 patients and of these, 20 had juvenile myelomonocytic leukemia (JMML). The disorder was named ”CBL syndrome” or ”Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia” (NSLL). To date, prenatal abnormalities have not been reported and it is still debated whether the CBL syndrome falls into the category of a RASopathy, or represents a diferent entity. Here we report on three unrelated patients with CBL mutations manifesting with hydrops fetalis, fetal pleural efusions and/or congenital hydro-/chylothorax. Our fndings further connect the CBL syndrome with the RASopathies. DOI: https://doi.org/10.1002/ajmg.a.36838 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-104644 Journal Article Published Version Originally published at: Bülow, Luzie; Lissewski, Christina; Bressel, Rainer; Rauch, Anita; Stark, Zornitza; Zenker, Martin; Bartsch, Oliver (2014). Hydrops, fetal pleural efusions and chylothorax in three patients with CBL mutations. American Journal of Medical Genetics. Part A, 167(2):394-399. DOI: https://doi.org/10.1002/ajmg.a.36838
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Zurich Open Repository andArchiveUniversity of ZurichMain LibraryStrickhofstrasse 39CH-8057 Zurichwww.zora.uzh.ch
Year: 2014
Hydrops, fetal pleural effusions and chylothorax in three patients with CBLmutations
Bülow, Luzie ; Lissewski, Christina ; Bressel, Rainer ; Rauch, Anita ; Stark, Zornitza ; Zenker, Martin ;Bartsch, Oliver
Abstract: Fetal hydrops, fetal pleural effusions, hydrothorax, and chylothorax, may be associated withvarious genetic disorders, in particular with the Noonan, cardio-facio-cutaneous and Costello syndromes.These syndromes, collectively called RASopathies, are caused by mutations in the RAS/MAPK pathway,which is known to play a major role in lymphangiogenesis. Recently, germline mutations in the CasitasB-cell lymphoma (CBL) gene were reported in 25 patients and of these, 20 had juvenile myelomonocyticleukemia (JMML). The disorder was named ”CBL syndrome” or ”Noonan syndrome-like disorder withor without juvenile myelomonocytic leukemia” (NSLL). To date, prenatal abnormalities have not beenreported and it is still debated whether the CBL syndrome falls into the category of a RASopathy, orrepresents a different entity. Here we report on three unrelated patients with CBL mutations manifestingwith hydrops fetalis, fetal pleural effusions and/or congenital hydro-/chylothorax. Our findings furtherconnect the CBL syndrome with the RASopathies.
DOI: https://doi.org/10.1002/ajmg.a.36838
Posted at the Zurich Open Repository and Archive, University of ZurichZORA URL: https://doi.org/10.5167/uzh-104644Journal ArticlePublished Version
Originally published at:Bülow, Luzie; Lissewski, Christina; Bressel, Rainer; Rauch, Anita; Stark, Zornitza; Zenker, Martin;Bartsch, Oliver (2014). Hydrops, fetal pleural effusions and chylothorax in three patients with CBLmutations. American Journal of Medical Genetics. Part A, 167(2):394-399.DOI: https://doi.org/10.1002/ajmg.a.36838
CLINICAL REPORT
Hydrops, Fetal Pleural Effusions and Chylothoraxin Three Patients With CBL MutationsLuzie Bulow,1 Christina Lissewski,2 Rainer Bressel,3 Anita Rauch,4 Zornitza Stark,5
Martin Zenker,2 and Oliver Bartsch1*1Institute of Human Genetics, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
2Institute of Human Genetics, University Hospital, Magdeburg, Germany
3Pediatric Practice, Groß-Gerau, Germany
4Institute of Medical Genetics, University of Zurich, Schlieren-Zurich, Switzerland
5Victorian Clinical Genetics Services and Murdoch Children’s Research Institute, Melbourne, Australia
Manuscript Received: 5 June 2014; Manuscript Accepted: 27 September 2014
Fetal hydrops, fetal pleural effusions, hydrothorax, and chylo-
thorax, may be associated with various genetic disorders, in
to be included in the differential diagnosis of fetal pleural effusions,hydrops fetalis, and probably also fetal nuchal edema.
ACKNOWLEDGMENTS
We thank the families for their consent and numerous colleagues
for their clinical work.
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