, Volume 10, Issue 4, pp 363-369
Date: 27 May 2009

Alu-specific microhomology-mediated deletions in CDKL5 in females with early-onset seizure disorder

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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.

Ayelet Erez and Amina J. Patel contributed equally to this work.