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From the Neurogenetics Group (L.D., K.G.C., L.R.F.C., A.S., D.A., T.V.D., P.D.) and Applied Molecular Genomics Group (D.G., J.D.), Department of Molecular Genetics, VIB; Laboratory of Neurogenetics (L.D., K.G.C., L.R.F.C., A.S., D.A., T.V.D., P.D.), Institute Born-Bunge; University of Antwerp (L.D., L.R.F.C., A.S., D.A., T.V.D., D.G., J.D., P.D.), Antwerpen; Department of Neurology (K.P., W.V.P.), University Hospital Gasthuisberg, Katholieke Universiteit Leuven; and Division of Neurology (K.G.C., P.D.), University Hospital of Antwerp, Antwerpen, Belgium.
* To whom correspondence should be addressed. E-mail: peter.dejonghe{at}ua.ac.be.
Abstract Objective: To map the disease-causing locus in a large Belgian family with occipitotemporal lobe epilepsy associated with migraine with visual aura and to describe the clinical, electrophysiologic, and imaging characteristics. Methods: DNA samples from 21 family members were obtained and an 8 cM density genome-wide scan was performed. The authors interviewed 21 individuals and performed interictal EEG in 14 and brain MRI in 13 individuals. Results: Nine at risk family members and one deceased individual had epilepsy with occipital and temporal lobe symptomatology, variable age at onset, usually good prognosis, no epileptic EEG features, and normal brain MRI. Five of the 10 patients had a history of migraine with aura (p = 0.0026). Seizures and migraine attacks occurred as separate episodes in all but one patient. Three patients described light flashes both as epileptic and migraine aura. Epilepsy and migraine started at the same age in three patients and remitted simultaneously in two. The epileptic phenotype had a dominant mode of inheritance with a reduced penetrance of 75%. A conclusive two-point lod score of 3.3 was obtained for marker D9S257 at recombination fraction zero. Haplotype analysis defined a candidate region of 9.95 cM (5.96 Mb) between markers GATA152H04 and D9S253 located at chromosome 9q21-q22 based upon recombinations in affected individuals. Conclusions: The clinical association in this family of occipitotemporal lobe epilepsy and migraine with visual aura and the conclusive linkage of the occipitotemporal lobe epilepsy/migraine with aura trait to a single locus suggests a common monogenic gene defect.
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