Alu-specific microhomology-mediated deletions in CDKL5 in females with early-onset seizure disorder.
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.
Erez
Ayelet
A
Department of Molecular & Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Patel
Amina J
AJ
Wang
Xueqing
X
Xia
Zhilian
Z
Bhatt
Samarth S
SS
Craigen
William
W
Cheung
Sau Wai
SW
Lewis
Richard A
RA
Fang
Ping
P
Davenport
Sandra L H
SL
Stankiewicz
Pawel
P
Lalani
Seema R
SR
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
D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human