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Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate
  1. F Laumonnier1,*,
  2. S Holbert1,*,
  3. N Ronce1,
  4. F Faravelli2,
  5. S Lenzner3,
  6. C E Schwartz4,
  7. J Lespinasse5,
  8. H Van Esch6,
  9. D Lacombe7,
  10. C Goizet7,
  11. F Phan-Dinh Tuy8,
  12. H van Bokhoven9,
  13. J-P Fryns6,
  14. J Chelly8,
  15. H-H Ropers3,
  16. C Moraine1,
  17. B C J Hamel9,
  18. S Briault1
  1. 1INSERM U619 “Génétique de l’autisme et des déficiences mentales”, Faculté de Médecine, Université François Rabelais, Tours, France
  2. 2Genetica Umana, Ospedale Galliera, Genova, Italy
  3. 3Max-Planck-Institute for Molecular Genetics, Berlin, Germany
  4. 4Greenwood Genetic Center, Gregor Mendel Circle, Greenwood, South Carolina, USA
  5. 5Laboratoire de Génétique Chromosomique, CH Chambéry, France
  6. 6Centre for Human Genetics, University of Leuven, Belgium
  7. 7Department of Medical Genetics, CHU Pellegrin, Bordeaux, France
  8. 8Institut Cochin, CHU Cochin, Paris, France
  9. 9Department of Human Genetics, University Medical Centre, Nijmegen, Netherlands
  1. Correspondence to:
 Dr Sylvain Briault
 INSERM U619, Génétique de l’autisme et des déficiences mentales, Faculté de Médecine 10, Bd Tonnellé BP 3223, 37032 Tours cedex 1, France;


Truncating mutations were found in the PHF8 gene (encoding the PHD finger protein 8) in two unrelated families with X linked mental retardation (XLMR) associated with cleft lip/palate (MIM 300263). Expression studies showed that this gene is ubiquitously transcribed, with strong expression of the mouse orthologue Phf8 in embryonic and adult brain structures. The coded PHF8 protein harbours two functional domains, a PHD finger and a JmjC (Jumonji-like C terminus) domain, implicating it in transcriptional regulation and chromatin remodelling. The association of XLMR and cleft lip/palate in these patients with mutations in PHF8 suggests an important function of PHF8 in midline formation and in the development of cognitive abilities, and links this gene to XLMR associated with cleft lip/palate. Further studies will explore the specific mechanisms whereby PHF8 alterations lead to mental retardation and midline defects.

  • DHPLC, denaturing high performance liquid chromatography
  • FISH, fluorescence in situ hybridisation
  • MRX, non-syndromic forms of X linked mental retardation
  • MRXS, syndromic forms of X linked mental retardation
  • XLMR, X linked mental retardation
  • X linked mental retardation
  • cleft lip/palate
  • PHD finger protein
  • PHF8 mutations

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  • * These authors contributed equally to the work

  • Competing interests: none declared