neurogenetics

, Volume 10, Issue 4, pp 363–369

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

  • 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
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 spasmsCDKL5Alu-mediated deletionsXp22.13 region

Supplementary material

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

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Ayelet Erez
    • 1
  • Amina J. Patel
    • 1
  • Xueqing Wang
    • 1
  • Zhilian Xia
    • 1
  • Samarth S. Bhatt
    • 1
  • William Craigen
    • 1
  • Sau Wai Cheung
    • 1
  • Richard A. Lewis
    • 1
    • 2
    • 3
    • 4
  • Ping Fang
    • 1
  • Sandra L. H. Davenport
    • 5
  • Pawel Stankiewicz
    • 6
  • Seema R. Lalani
    • 1
  1. 1.Department of Molecular & Human GeneticsBaylor College of MedicineHoustonUSA
  2. 2.Department of OphthalmologyBaylor College of MedicineHoustonUSA
  3. 3.Department of MedicineBaylor College of MedicineHoustonUSA
  4. 4.Department of PediatricsBaylor College of MedicineHoustonUSA
  5. 5.Sensory Genetics and NeurodevelopmentBloomingtonUSA
  6. 6.Department of Molecular & Human GeneticsBaylor College of MedicineHoustonUSA