neurogenetics

, Volume 10, Issue 4, pp 363–369

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

Authors

  • Ayelet Erez
    • Department of Molecular & Human GeneticsBaylor College of Medicine
  • Amina J. Patel
    • Department of Molecular & Human GeneticsBaylor College of Medicine
  • Xueqing Wang
    • Department of Molecular & Human GeneticsBaylor College of Medicine
  • Zhilian Xia
    • Department of Molecular & Human GeneticsBaylor College of Medicine
  • Samarth S. Bhatt
    • Department of Molecular & Human GeneticsBaylor College of Medicine
  • William Craigen
    • Department of Molecular & Human GeneticsBaylor College of Medicine
  • Sau Wai Cheung
    • Department of Molecular & Human GeneticsBaylor College of Medicine
  • Richard A. Lewis
    • Department of Molecular & Human GeneticsBaylor College of Medicine
    • Department of OphthalmologyBaylor College of Medicine
    • Department of MedicineBaylor College of Medicine
    • Department of PediatricsBaylor College of Medicine
  • Ping Fang
    • Department of Molecular & Human GeneticsBaylor College of Medicine
  • Sandra L. H. Davenport
    • Sensory Genetics and Neurodevelopment
    • Department of Molecular & Human GeneticsBaylor College of Medicine
  • Seema R. Lalani
    • Department of Molecular & Human GeneticsBaylor College of Medicine
SHORT COMMUNICATION

DOI: 10.1007/s10048-009-0195-z

Cite this article as:
Erez, A., Patel, A.J., Wang, X. et al. Neurogenetics (2009) 10: 363. doi:10.1007/s10048-009-0195-z

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.

Keywords

Infantile spasms CDKL5 Alu-mediated deletions Xp22.13 region

Supplementary material

10048_2009_195_MOESM1_ESM.pdf (314 kb)
ESM 1 (PDF 314 kb)

Copyright information

© Springer-Verlag 2009