These authors contributed equally to this work.
Identification of genomic deletions spanning the PCDH19 gene in two unrelated girls with intellectual disability and seizures
Article first published online: 13 DEC 2011
© 2011 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Volume 82, Issue 6, pages 540–545, December 2012
How to Cite
Vincent, A., Noor, A., Janson, A., Minassian, B., Ayub, M., Vincent, J. and Morel, C. (2012), Identification of genomic deletions spanning the PCDH19 gene in two unrelated girls with intellectual disability and seizures. Clinical Genetics, 82: 540–545. doi: 10.1111/j.1399-0004.2011.01812.x
- Issue published online: 6 NOV 2012
- Article first published online: 13 DEC 2011
- Accepted manuscript online: 17 NOV 2011 12:56PM EST
- Received 8 August 2011, revised and accepted for publication 14 November 2011
- intellectual disability (ID);
- X-linked disorder;
Vincent AK, Noor A, Janson A, Minassian BA, Ayub M, Vincent JB, Morel CF. Identification of genomic deletions spanning the PCDH19 gene in two unrelated girls with intellectual disability and seizures.
Recently, missense and truncating mutations in the gene PCDH19 have been reported to cause female-restricted epilepsy with mental retardation (EFMR). EFMR (MIM#300088) is an X-linked disorder characterized by early onset seizures and intellectual disability (ID). Interestingly, unlike typical X-linked mode of inheritance, the phenotype is restricted to females, and males are unaffected carriers. PCDH19 is highly expressed in brain, and the encoded protein belongs to the cadherin superfamily. Here we report two unrelated female patients with deletions spanning PCDH19 identified by copy number variation (CNV) analysis and validated by qPCR. In one, we have identified a 3 Mb interstitial deletion at Xq21.33-q22.1 which spans PCDH19, LOC442459 & TNMD. This patient had her first seizure at 8 months old, and also has ID and aggressive behavior. In another female patient we identified a de novo 603 kb heterozygous deletion in a female patient with fits (since 1 year of age), ID, hyperactivity and aggressive behavior. The deletion spans the entire PCDH19 gene (also TNMD, SRPX2, TSPAN6 and SYTL4). In conclusion, our results suggest that deletions at PCDH19 also cause EFMR.