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

作者：Erez Ayelet; Patel Amina J; Wang Xueqing; Xia Zhilian; Bhatt Samarth S; Craigen William; Cheung Sau Wai; Lewis Richard A; Fang Ping; Davenport Sandra L H; Stankiewicz Pawel^*; Lalani Seema R

来源：Neurogenetics, 2009, 10(4): 363-369.

DOI：10.1007/s10048-009-0195-z

• Infantile spasms
• CDKL5
• Alu-mediated deletions
• Xp22.13 region

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.

• 出版日期2009-10