Familial neonatal seizures with intellectual disability caused by a microduplication of chromosome 2q24.3.
A family with dominantly inherited neonatal seizures and intellectual disability was atypical for neonatal and infantile seizure syndromes associated with potassium (KCNQ2 and KCNQ3) and sodium (SCN2A) channel mutations. Microsatellite markers linked to KCNQ2, KCNQ3, and SCN2A were examined to exclude candidate locations, but instead revealed a duplication detected by observation of three alleles for two markers flanking SCN2A. Characterization revealed a 1.57 Mb duplication at 2q24.3 containing eight genes including SCN2A, SCN3A, and the 3¢ end of SCN1A. The duplication was partially inverted and inserted within or near SCN1A, probably affecting the expression levels of associated genes, including sodium channels. Rare or unique microchromosomal copy number mutations might underlie familial epilepsies that do not fit within the clinical criteria for the established syndromes.
Heron
Sarah E
SE
SA Pathology at Women's and Children's Hospital, Adelaide, South Australia, Australia. sarah.heron@adelaide.edu.au
Scheffer
Ingrid E
IE
Grinton
Bronwyn E
BE
Eyre
Helen
H
Oliver
Karen L
KL
Bain
Sharon
S
Berkovic
Samuel F
SF
Mulley
John C
JC
D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics; D020936:Epilepsy, Benign Neonatal / Q000235:genetics; D005190:Family; D005260:Female; D020440:Gene Duplication; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D051658:KCNQ2 Potassium Channel / Q000235:genetics / Q000378:metabolism; D051659:KCNQ3 Potassium Channel / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D010375:Pedigree; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D013577:Syndrome
D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568251:SCN2A protein, human; C424715:SCN3A protein, human; D015222:Sodium Channels