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Deletion of YWHAE in a patient with periventricular heterotopias and pronounced corpus callosum hypoplasia
  1. Cécile Mignon-Ravix1,2,
  2. Pierre Cacciagli3,
  3. Bilal El-Waly1,2,
  4. Anne Moncla1,2,3,
  5. Mathieu Milh1,2,4,
  6. Nadine Girard2,5,6,
  7. Brigitte Chabrol1,2,4,
  8. Nicole Philip1,2,3,
  9. Laurent Villard1,2
  1. 1Inserm, U910, Marseille, France
  2. 2Université de la Méditerranée, Faculté de Médecine, Marseille, France
  3. 3Département de Génétique Médicale, Hôpital d'Enfants de la Timone, Marseille, France
  4. 4Département de Neurologie Pédiatrique, Hôpital d'Enfants de La Timone, Marseille, France
  5. 5Département de Neuroradiologie, Hôpital d'Adultes de La Timone, Marseille, France
  6. 6CNRS, UMR6612, Marseille, France
  1. Correspondence to Dr Laurent Villard, Inserm UMR910, Faculté de Médecine Timone, 27 bd Jean Moulin, 13385 Marseille cedex 5, France; laurent.villard{at}


Background Malformations of cortical development are not rare and cause a wide spectrum of neurological diseases based on the affected region in the cerebral cortex. A significant proportion of these malformations could have a genetic basis. However, genetic studies are limited because most cases are sporadic and mendelian forms are rare.

Methods In order to identify new genetic causes in patients presenting defects of cortical organisation, array based comparative genomic hybridisation was performed in a cohort of 100 sporadic cases with various types of cortical malformations in search for inframicroscopic chromosomal rearrangements.

Results In one patient presenting with periventricular nodular heterotopias and pronounced corpus callosum hypoplasia, a small (400 kb) 17p13.3 deletion involving the YWHAE gene was identified. It is shown that YWHAE is the only brain expressed gene in the deleted region and that the other genes in the interval are unlikely to contribute to the brain malformation phenotype of this patient.

Conclusion Most 17p13.3 deletions reported to date are large, such as the deletions causing Miller–Dieker syndrome, and involve several genes implicated in various steps of brain development. Haploinsufficiency of the mouse orthologue of YWHAE causes a defect of neuronal migration. However, the human counterpart of this phenotype was not known. The case described here represents the smallest reported deletion involving the YWHAE gene and could represent the human counterpart of the abnormal cortical organisation phenotype presented by the Ywhae heterozygous knockout mouse.

  • 17p13.3 deletion
  • Miller-Dieker syndrome
  • malformations of cortical development
  • comparative genomic hybridisation
  • genetics
  • molecular genetics
  • neurology

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  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the CPP Marseille.

  • Patients consent Not required.

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