PT  - JOURNAL ARTICLE
AU  - Mignon-Ravix, Cécile
AU  - Cacciagli, Pierre
AU  - El-Waly, Bilal
AU  - Moncla, Anne
AU  - Milh, Mathieu
AU  - Girard, Nadine
AU  - Chabrol, Brigitte
AU  - Philip, Nicole
AU  - Villard, Laurent
TI  - Deletion of <em>YWHAE</em> in a patient with periventricular heterotopias and pronounced corpus callosum hypoplasia
AID  - 10.1136/jmg.2009.069112
DP  - 2010 Feb 01
TA  - Journal of Medical Genetics
PG  - 132--136
VI  - 47
IP  - 2
4099  - http://jmg.bmj.com/content/47/2/132.short
4100  - http://jmg.bmj.com/content/47/2/132.full
SO  - J Med Genet2010 Feb 01; 47
AB  - 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.