Abstract
Lymphedema, lymphangiectasias, mental retardation and unusual facial characteristics define the autosomal recessive Hennekam syndrome. Homozygosity mapping identified a critical chromosomal region containing CCBE1, the human ortholog of a gene essential for lymphangiogenesis in zebrafish. Homozygous and compound heterozygous mutations in seven subjects paired with functional analysis in a zebrafish model identify CCBE1 as one of few genes causing primary generalized lymph-vessel dysplasia in humans.
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Acknowledgements
S.S.-M. and E.G. were supported by the Koninklijke Nederlandse Akademie van Wetenschappen, B.M.H. by an Australian National Health and Medical Research Council CJ Martin Fellowship. M.J. Van De Vijver (Academic Medical Centre Amsterdam) provided gut biopsies of controls and H. Begthel (Hubrecht Institute, Utrecht) performed histology. T. Nilsson (McGill University) generously provided the GalNAc-T2GFP cell line and A. Akhmanova (Erasmus Medical Center, Rotterdam) the NPY:mVenus cell line. We are grateful to the subjects and their families for their cooperation.
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L.A.-G., E.E.H., M.F.M., T.E.P., E.J.S., J.B.G.M.V., P.J.Z. and R.C.H. analyzed affected individuals, and E.A.H. performed genealogical studies. M.A., F.S., M.M.A.M.M., M.V., B.M.H., E.G., G.J.A.O., M.W. and S.S.-M. carried out experiments and analyzed data. S.S.-M. supervised the zebrafish experiments, and R.C.H. supervised the clinical and molecular studies and initiated the study. M.A., S.S.-M. and R.C.H. wrote the manuscript.
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The KNAW has filed a patent on human CCBE1.[AU: (i) Spell out KNAW please. (ii) Please specify CCBE1 protein or CCBE1 nucleic acid.]
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Alders, M., Hogan, B., Gjini, E. et al. Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans. Nat Genet 41, 1272–1274 (2009). https://doi.org/10.1038/ng.484
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DOI: https://doi.org/10.1038/ng.484
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