Stefano Sartori and Gabriella Di Rosa contributed equally to this work.
Article first published online: 22 JAN 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 2, pages 232–236, February 2009
How to Cite
Sartori, S., Di Rosa, G., Polli, R., Bettella, E., Tricomi, G., Tortorella, G. and Murgia, A. (2009), A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome. Am. J. Med. Genet., 149A: 232–236. doi: 10.1002/ajmg.a.32606
How to cite this article: Sartori S, Di Rosa G, Polli R, Bettella E, Tricomi G, Tortorella G, Murgia A. 2009. A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome. Am J Med Genet Part A 149A:232–236.
- Issue published online: 22 JAN 2009
- Article first published online: 22 JAN 2009
- Manuscript Accepted: 1 OCT 2008
- Manuscript Received: 26 JUN 2008
- early-onset epileptic encephalopathy;
- Rett syndrome variant;
- Klinefelter syndrome;
- X-chromosome inactivation;
- 47,XXY karyotype
Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein. The resulting phenotype is characterized by a severe early-onset epileptic encephalopathy, global developmental delay, and profound intellectual and motor impairment with features reminiscent of Rett syndrome. In light of the data presented we discuss the possible phenotypic modulatory effects of the supernumerary wild type X allele and pattern of X chromosome inactivation and stress the importance of considering the causal involvement of CDKL5 in developmentally delayed males with early-onset seizures. © 2009 Wiley-Liss, Inc.