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Two Novel Epilepsy-Linked Mutations Leading to a Loss of Function of LGI1
Elodie Chabrol, MS;
Cyprian Popescu, MD;
Isabelle Gourfinkel-An, MD, PhD;
Oriane Trouillard;
Christel Depienne, PhD;
Kristen Senechal, PhD;
Michel Baulac, MD;
Eric LeGuern, MD, PhD;
Stéphanie Baulac, PhD
Arch Neurol. 2007;64(2):217-222.
Background Mutations in the leucine-rich, glioma-inactivated 1 (LGI1) gene have been implicated in autosomal dominant lateral temporal epilepsy.
Objective To describe the clinical and genetic findings in 2 families with autosomal dominant lateral temporal epilepsy and the functional consequences of 2 novel mutations in LGI1.
Design Clinical, genetic, and functional investigations.
Setting University hospital.
Patients Two French families with autosomal dominant lateral temporal epilepsy.
Main Outcome Measure Mutation analysis.
Results Two novel disease-linked mutations, p.Leu232Pro and c.431 + 1G>A, were identified in LGI1. We demonstrated that the c.431 + 1G>A mutation causes the deletion of exons 3 and 4 of the LGI1 transcript and showed that the p.Leu232Pro mutation dramatically decreases secretion of the mutant protein by mammalian cells.
Conclusion Our data indicate that LGI1 is a secreted protein and suggest that LGI1-related epilepsy results from a loss of function.
Author Affiliations: INSEREM UMR 679 (Institut National de la Santé et de la Récherche Médicale, Unité Médicale Récherche 679), Neurologie and Thérapeutique Expérimentale, Université Pierre et Marie Curie-Paris 6, Faculté de Médecine (Ms Chabrol and Drs Popescu, Gourfinkel-An, Depienne, LeGuern, and S. Baulac), Center of Epileptology (Drs Popescu, Gourfinkel-An, and M. Baulac), and Department of Genetics, Cytogenetics, and Embryology (Ms Trouillard and Drs Depienne and LeGuern), Assistance Publique–Hôpitaux de Paris, Hôpital de la Pitié–Salpêtrière, Paris, France; and Department of Molecular Genetics, M. D. Anderson Cancer Center, Houston, Tex (Dr Senechal).
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