Abstracts

Rationale: Advances in narrowing probe space of DNA sequences through genic and intergenic regions enables array comparative genomic hybridization (aCGH) as a useful tool to localize chromosome mutation. We applied the technique to identify the mutation in an east-Taiwan aboriginal family with epilepsy. Methods: A detailed family pedigree was constructed by collecting clinical histories on all affected and unaffected individuals and their spouses. Blood samples were collected from 12 members (6 individuals with epilepsy). When karyotyping analysis did not show abnormality, human whole genome aCGH was carried out to measure the copy number differences in DNA. Then real-time polymerase chain reaction (real-time PCR) was performed to quantitate the fold change in the target genes. Results: We obtained genealogical information on 25 family members (including 5 spouses) and retrospectively reviewed the clinical studies from 4 individuals. Blood samples were collected from 12 members (7 individuals with epilepsy). Proband III-1 and IV-4 had habitual complex partial seizures. Proband II-2 and IV-4 were known to have rare generalized seizures. Proband IV-2 had 2 febrile seizures. Proband II-3 and II-6 had rare undetermined seizures. A constant copy number change in chromosome 14q11.1-11.2 was identified in affected individuals. Statistical fold change of two genes (OR4K2 and OR4K3 locate at 14q11.2) in all affected individuals was obtained. Conclusions: In this family, the variety of epileptic seizure manifestations and different comorbidity led to difficult categorization of epilepsy syndrome. However, a new candidate locus for familial epilepsy is mapped on chromosome 14.11-11.2. The study approved aCGH as a useful tool for identifying genetic changes in epilepsy patients with familiality.