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MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations
  1. N Le Meur1,2,
  2. M Holder-Espinasse3,
  3. S Jaillard4,5,
  4. A Goldenberg1,
  5. S Joriot6,
  6. P Amati-Bonneau7,8,
  7. A Guichet7,
  8. M Barth7,
  9. A Charollais9,
  10. H Journel10,
  11. S Auvin11,
  12. C Boucher1,
  13. J-P Kerckaert12,
  14. V David5,13,
  15. S Manouvrier-Hanu3,
  16. P Saugier-Veber1,14,
  17. T Frébourg1,14,
  18. C Dubourg5,13,
  19. J Andrieux15,
  20. D Bonneau7,8
  1. 1Service de Génétique, CHU de Rouen, France
  2. 2Laboratoire de Cytogénétique, EFS-Normandie, Bois-Guillaume, France
  3. 3Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU de Lille, France
  4. 4Laboratoire de Cytogénétique, CHU Pontchaillou, Rennes, France
  5. 5CNRS UMR 6061, Université de Rennes 1, IFR 140, Rennes, France
  6. 6Service de Neuropédiatrie, Hôpital Roger Salengro, CHRU de Lille, France
  7. 7Service de Génétique Médicale, CHU d'Angers, France
  8. 8Inserm U694, Université d'Angers, France
  9. 9Service de Médecine Néonatale, CHU de Rouen, France
  10. 10Service de Génétique Clinique, Centre Hospitalier Bretagne Atlantique, Vannes, France
  11. 11Service de Neurologie Pédiatrique, CHU Robert Debré - APHP, Paris, France
  12. 12Plateforme de Génomique Fonctionnelle, Université de Lille II, France
  13. 13Laboratoire de Génétique Moléculaire, CHU Pontchaillou, Rennes, France
  14. 14Inserm U614, IHU, Université de Rouen, France
  15. 15Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre, CHRU de Lille, France
  1. Correspondence to Dr N Le Meur, Laboratoire de Cytogénétique, EFS-Normandie, Bois-Guillaume, France; nathalie.lemeur{at}


Background Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved our ability to detect cryptic unbalanced rearrangements in patients with syndromic mental retardation.

Method Molecular karyotyping of six patients with syndromic mental retardation was carried out using whole-genome oligonucleotide array-CGH.

Results 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe mental retardation with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified.

Conclusion Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations.

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  • Supplementary methods are published online at

  • Competing interests None.

  • Ethics approval Obtained.

  • Patient consent Parental consent obtained.

  • Provenance and Peer review Not commissioned; externally peer reviewed.