Erschienen in:
01.10.2009 | SHORT COMMUNICATION
Alu-specific microhomology-mediated deletions in CDKL5 in females with early-onset seizure disorder
verfasst von:
Ayelet Erez, Amina J. Patel, Xueqing Wang, Zhilian Xia, Samarth S. Bhatt, William Craigen, Sau Wai Cheung, Richard A. Lewis, Ping Fang, Sandra L. H. Davenport, Pawel Stankiewicz, Seema R. Lalani
Erschienen in:
Neurogenetics
|
Ausgabe 4/2009
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Abstract
Mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene in Xp22.13 have been associated with infantile spasms, early-onset intractable epilepsy, and a Rett syndrome (RTT)-like phenotype. Using array comparative genomic hybridization, we identified variable-sized microdeletions involving exons 1–4 of the CDKL5 gene in three females with early-onset seizures. Two of these deletions were flanked by Alu repetitive elements and may have resulted from either non-allelic homologous recombination or the microhomology-mediated Fork Stalling and Template Switching/Microhomology-Mediated Break-Induced Replication mechanism. Our findings demonstrate the first instance of genomic deletion as the molecular basis of CDKL5 deficiency in females and highlight the importance of exon targeted array-CGH analysis for this gene in females with drug-resistant early-onset seizures.