title: Alu-specific microhomology-mediated deletions in CDKL5 in females with early-onset seizure disorder.
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.
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Erez
authors.forename: Amina J
authors.initials: AJ
authors.lastname: Patel
authors.forename: Xueqing
authors.initials: X
authors.lastname: Wang
authors.forename: Zhilian
authors.initials: Z
authors.lastname: Xia
authors.forename: Samarth S
authors.initials: SS
authors.lastname: Bhatt
authors.forename: William
authors.initials: W
authors.lastname: Craigen
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lewis
authors.forename: Ping
authors.initials: P
authors.lastname: Fang
authors.forename: Sandra L H
authors.initials: SL
authors.lastname: Davenport
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Seema R
authors.initials: SR
authors.lastname: Lalani
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D017668:Age of Onset; D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015518:Rett Syndrome / Q000235:genetics / Q000503:physiopathology; D012640:Seizures / Q000235:genetics / Q000503:physiopathology; D017384:Sequence Deletion; D049951:X Chromosome Inactivation; D055815:Young Adult
chemical_list: D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human