Brief Communication abstract


Nature Genetics 39, 963 - 965 (2007)
Published online: 15 July 2007 | doi:10.1038/ng2083

Mutations in RNF135, a gene within the NF1 microdeletion region, cause phenotypic abnormalities including overgrowth

Jenny Douglas1,11, Deirdre Cilliers1,11, Kim Coleman1, Katrina Tatton-Brown1,2, Karen Barker1, Brigitte Bernhard3, John Burn3, Susan Huson4, Dragana Josifova5, Didier Lacombe6, Mohsin Malik7, Sahar Mansour2, Evan Reid8, Valerie Cormier-Daire9, Trevor Cole10, The Childhood Overgrowth Collaboration & Nazneen Rahman1

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17q11 microdeletions that encompass NF1 cause 5%–10% of cases of neurofibromatosis type 1, and individuals with microdeletions are typically taller than individuals with intragenic NF1 mutations, suggesting that deletion of a neighboring gene might promote human growth. We identified mutations in RNF135, which is within the NF1 microdeletion region, in six families characterized by overgrowth, learning disability, dysmorphic features and variable additional features. These data identify RNF135 as causative of a new overgrowth syndrome and demonstrate that RNF135 haploinsufficiency contributes to the phenotype of NF1 microdeletion cases.

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  1. Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
  2. S.W. Thames Regional Genetics Service, St. George's Hospital Medical School, London SW17 0RE, UK.
  3. Institute of Human Genetics, International Centre for Life, Newcastle Upon Tyne NE1 3BZ, UK.
  4. Department of Medical Genetics, St. Mary's Hospital, Manchester M13 OJH, UK.
  5. Department of Clinical Genetics, Guy's Hospital, London SE1 9RT, UK.
  6. Department of Medical Genetics, Hopital Pellegrin-enfants, EA2406 Bordeaux, France.
  7. Queen Elizabeth the Queen Mother's Hospital, Margate CT9 4AN, UK.
  8. Medical Genetics Department, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
  9. Department of Medical Genetics, Hopital Necker Enfants Malades, 75015 Paris, France.
  10. Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham B15 2TG, UK.
  11. These authors contributed equally to this work.

Correspondence to: Nazneen Rahman1 e-mail: nazneen.rahman@icr.ac.uk


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