Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance

TY - JOUR

T1 - Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance

AU - Dibbens, Leanne M

AU - Mullen, Saul

AU - Helbig, Ingo

AU - Mefford, Heather C

AU - Bayly, Marta A

AU - Bellows, Susannah

AU - Leu, Costin

AU - Trucks, Holger

AU - Obermeier, Tanja

AU - Wittig, Michael

AU - Franke, Andre

AU - Caglayan, Hande

AU - Yapici, Zuhal

AU - EPICURE Consortium

AU - Sander, Thomas

AU - Eichler, Evan E

AU - Scheffer, Ingrid E

AU - Mulley, John C

AU - Berkovic, Samuel F

AU - Møller, Rikke Steensbjerre

N1 - Keywords: Chromosome Deletion; Chromosomes, Human, Pair 15; Cohort Studies; Epilepsy; European Continental Ancestry Group; Female; Genetic Predisposition to Disease; Humans; Male; Pedigree

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1093/hmg/ddp311

DO - 10.1093/hmg/ddp311

M3 - Journal article

C2 - 19592580

SN - 0964-6906

VL - 18

SP - 3626

EP - 3631

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 19

ER -