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.
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.
Authors: Gary A Heiman; Kay Kamberakis; Richard Gill; Sergey Kalachikov; Timothy A Pedley; W Allen Hauser; Ruth Ottman Journal: Epilepsia Date: 2010-07-26 Impact factor: 5.864
Authors: Michael Seagar; Michael Russier; Olivier Caillard; Yves Maulet; Laure Fronzaroli-Molinieres; Marina De San Feliciano; Norah Boumedine-Guignon; Léa Rodriguez; Mickael Zbili; Fabrice Usseglio; Christine Formisano-Tréziny; Fahamoe Youssouf; Marion Sangiardi; Morgane Boillot; Stéphanie Baulac; María José Benitez; Juan-José Garrido; Dominique Debanne; Oussama El Far Journal: Proc Natl Acad Sci U S A Date: 2017-07-03 Impact factor: 11.205
Authors: Elodie Chabrol; Vincent Navarro; Giovanni Provenzano; Ivan Cohen; Céline Dinocourt; Sophie Rivaud-Péchoux; Desdemona Fricker; Michel Baulac; Richard Miles; Eric Leguern; Stéphanie Baulac Journal: Brain Date: 2010-07-21 Impact factor: 13.501