Brief Communication abstract

Nature Genetics 41, 1272 - 1274 (2009)
Published online: 22 November 2009 | doi:10.1038/ng.484

Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans

Marielle Alders1, Benjamin M Hogan2, Evisa Gjini2, Faranak Salehi1, Lihadh Al-Gazali3, Eric A Hennekam4, Eva E Holmberg5, Marcel M A M Mannens1, Margot F Mulder6, G Johan A Offerhaus7,8, Trine E Prescott5, Eelco J Schroor9, Joke B G M Verheij10, Merlijn Witte2, Petra J Zwijnenburg11,14, Mikka Vikkula12, Stefan Schulte-Merker2,15 & Raoul C Hennekam13,14,15


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.

  1. Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands.
  2. Hubrecht Institute – Koninklijke Nederlandse Akademie van Wetenschappen and University Medical Centre, Utrecht, The Netherlands.
  3. Department of Paediatrics and Pathology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
  4. Department of Clinical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
  5. Department of Medical Genetics, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  6. Department of Pediatrics, Free University Medical Center, Amsterdam, The Netherlands.
  7. Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands.
  8. Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
  9. Department of Pediatrics Amalia, Isala Clinics, Zwolle, The Netherlands.
  10. Department of Clinical Genetics, University Medical Centre Groningen, Groningen, The Netherlands.
  11. Department of Clinical Genetics, Free University Medical Center, Amsterdam, The Netherlands.
  12. Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
  13. Clinical and Molecular Genetics Unit, Institute of Child Health, Great Ormond Street Hospital for Children, University College London, London, UK.
  14. Department of Pediatrics, Academic Medical Centre, Amsterdam, The Netherlands.
  15. These authors contributed equally to this work.

Correspondence to: Raoul C Hennekam13,14,15 e-mail:


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