Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance.
Microdeletion at chromosomal position 15q13.3 has been described in intellectual disability, autism spectrum disorders, schizophrenia and recently in idiopathic generalized epilepsy (IGE). Using independent IGE cohorts, we first aimed to confirm the association of 15q13.3 deletions and IGE. We then set out to determine the relative occurrence of sporadic and familial cases and to examine the likelihood of having seizures for individuals with the microdeletion in familial cases. The 15q13.3 microdeletion was identified in 7 of 539 (1.3%) unrelated cases of IGE using quantitative PCR or SNP arrays and confirmed by array comparative genomic hybridization analysis using probes specific to the 15q13.3 region. The inheritance of this lesion was tracked using family studies. Of the seven microdeletions identified in probands, three were de novo, two were transmitted from an unaffected parent and in two cases the parents were unavailable. Non-penetrance of the microdeletion was identified in 4/7 pedigrees and three pedigrees included other family members with IGE who lacked the 15q13.3 deletion. The odds ratio is 68 (95% confidence interval 29-181), indicating a pathogenic lesion predisposing to epilepsy with complex inheritance and incomplete penetrance for the IGE component of the phenotype in multiplex families.
Dibbens
Leanne M
LM
Epilepsy Research Program, SA Pathology at Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia. leanne.dibbens@health.sa.gov.au
Mullen
Saul
S
Helbig
Ingo
I
Mefford
Heather C
HC
Bayly
Marta A
MA
Bellows
Susannah
S
Leu
Costin
C
Trucks
Holger
H
Obermeier
Tanja
T
Wittig
Michael
M
Franke
Andre
A
Caglayan
Hande
H
Yapici
Zuhal
Z
Sander
Thomas
T
Eichler
Evan E
EE
Scheffer
Ingrid E
IE
Mulley
John C
JC
Berkovic
Samuel F
SF
D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D015331:Cohort Studies; D004827:Epilepsy / Q000151:congenital / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010375:Pedigree; D044465:White People / Q000235:genetics