title: Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance.
abstract: 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.
authors: Epilepsy Research Program, SA Pathology at Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia. leanne.dibbens@health.sa.gov.au
authors: Leanne M
authors: LM
authors: Dibbens
authors: Saul
authors: S
authors: Mullen
authors: Ingo
authors: I
authors: Helbig
authors: Heather C
authors: HC
authors: Mefford
authors: Marta A
authors: MA
authors: Bayly
authors: Susannah
authors: S
authors: Bellows
authors: Costin
authors: C
authors: Leu
authors: Holger
authors: H
authors: Trucks
authors: Tanja
authors: T
authors: Obermeier
authors: Michael
authors: M
authors: Wittig
authors: Andre
authors: A
authors: Franke
authors: Hande
authors: H
authors: Caglayan
authors: Zuhal
authors: Z
authors: Yapici
authors: Thomas
authors: T
authors: Sander
authors: Evan E
authors: EE
authors: Eichler
authors: Ingrid E
authors: IE
authors: Scheffer
authors: John C
authors: JC
authors: Mulley
authors: Samuel F
authors: SF
authors: Berkovic
mesh_terms: 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