Homozygous PLCB1 deletion associated with malignant migrating partial seizures in infancy.
Malignant migrating partial seizures in infancy (MMPEI) is an early onset epileptic encephalopathy with few known etiologies. We sought to identify a novel cause of MMPEI in a child with MMPEI whose healthy parents were consanguineous. We used array comparative genomic hybridization (CGH) to identify copy number variants genome-wide and long-range polymerase chain reaction to further delineate the breakpoints of a deletion found by CGH. The proband had an inherited homozygous deletion of chromosome 20p13, disrupting the promoter region and first three coding exons of the gene PLCB1. Additional MMPEI cases were screened for similar deletions or mutations in PLCB1 but did not harbor mutations. Our results suggest that loss of PLCβ1 function is one cause of MMPEI, consistent with prior studies in a Plcb1 knockout mouse model that develops early onset epilepsy. We provide novel insight into the molecular mechanisms underlying MMPEI and further implicate PLCB1 as a candidate gene for severe childhood epilepsies. This work highlights the importance of pursuing genetic etiologies for severe early onset epilepsy syndromes.
Department of Neurology, Children's Hospital Boston, Boston, Massachusetts 02115, USA. annapurna.poduri@childrens.harvard.edu
Annapurna
A
Poduri
Sameer S
SS
Chopra
Edward G
EG
Neilan
P Christina
PC
Elhosary
Manju A
MA
Kurian
Esther
E
Meyer
Brenda J
BJ
Barry
Omar S
OS
Khwaja
Mustafa A M
MA
Salih
Tommy
T
Stödberg
Ingrid E
IE
Scheffer
Eamonn R
ER
Maher
Mustafa
M
Sahin
Bai-Lin
BL
Wu
Gerard T
GT
Berry
Christopher A
CA
Walsh
Jonathan
J
Picker
Sanjeev V
SV
Kothare
D004828:Epilepsies, Partial / Q000235:genetics*; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D054799:Phospholipase C beta / Q000235:genetics*
C518033:PLCB1 protein, human; D054799:Phospholipase C beta