Human Molecular Genetics Advance Access originally published online on July 10, 2009
Human Molecular Genetics 2009 18(19):3626-3631; doi:10.1093/hmg/ddp311
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Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance
1 Epilepsy Research Program, SA Pathology at Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia, 2 School of Paediatrics and Reproductive Health and 3 School of Molecular and Biomedical Sciences, University of Adelaide, South Australia 5005, Australia, 4 Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria 3081, Australia, 5 Department of Neuropediatrics, Institute for Clinical Molecular Biology, University Medical Center Schleswig-Holstein (Kiel Campus), Kiel 24105, Germany, 6 Department of Pediatrics and 7 Department of Genome Sciences, University of Washington, Seattle 98195, USA, 8 Cologne Center for Genomics, University of Cologne, Cologne, Germany, 9 EPICURE Consortium, 10 Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey, 11 Department of Child Neurology, Istanbul Medical School, Istanbul University, Istanbul, Turkey and 12 Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia
* To whom correspondence should be addressed. Tel: +61 881616711; Fax: +61 881617342; Email: leanne.dibbens{at}health.sa.gov.au
Received May 22, 2009; Revised June 23, 2009; Accepted July 2, 2009
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.
A list of participating centers of the EPICURE Consortium is provided in the Acknowledgements.
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