title: Autosomal dominant epilepsy with auditory features: a new LGI1 family including a phenocopy with cortical dysplasia.
abstract: We report a new family with autosomal dominant epilepsy with auditory features (ADEAF) including focal cortical dysplasia (FCD) in the proband. We aim to identify the molecular cause in this family and clarify the relationship between FCD and ADEAF. A large Iranian Jewish family including 14 individuals with epileptic seizures was phenotyped including high-resolution 3-T MRI. We performed linkage analysis and exome sequencing. LGI1, KANK1 and RELN were Sanger sequenced. Seizure semiology of 11 individuals was consistent with ADEAF. The proband underwent surgery for right mesiotemporal FCD. 3-T MRIs in four individuals were unremarkable. Linkage analysis revealed peaks on chromosome 9p24 (LOD 2.43) and 10q22-25 (LOD 2.04). A novel heterozygous LGI1 mutation was identified in all affected individuals except for the proband indicating a phenocopy. Exome sequencing did not reveal variants within the chromosome 9p24 region. Closely located variants in KANK1 and a RELN variant did not segregate with the phenotype. We provide detailed description of the phenotypic spectrum within a large ADEAF family with a novel LGI1 mutation that was conspicuously absent in the proband with FCD, demonstrating that despite identical clinical symptoms, phenocopies in ADEAF families may exist. This family illustrates that rare epilepsy syndromes within a single family can have both genetic and structural etiologies.
authors.affiliation: Department of Neurology, Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, University Hospital, Goethe-University Frankfurt, Frankfurt, Germany. k.klein@med.uni-frankfurt.de.|Department of Neurology, Epilepsy Center Hessen, University Hospitals Giessen and Marburg, Philipps-University Marburg, Marburg, Germany. k.klein@med.uni-frankfurt.de.
authors.forename: Karl Martin
authors.initials: KM
authors.lastname: Klein
authors.affiliation: Department of Neuropediatrics, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Pendziwiat
authors.affiliation: Schneider Children's Medical Center of Israel, Petach Tikva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Rony
authors.initials: R
authors.lastname: Cohen
authors.affiliation: Department of Neuropediatrics, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.|Core Unit Systems Medicine, University of Wuerzburg, Würzburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Appenzeller
authors.affiliation: Division Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Carolien G F
authors.initials: CG
authors.lastname: de Kovel
authors.affiliation: Department of Neurology, Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, University Hospital, Goethe-University Frankfurt, Frankfurt, Germany.|Department of Neurology, Epilepsy Center Hessen, University Hospitals Giessen and Marburg, Philipps-University Marburg, Marburg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Rosenow
authors.affiliation: Division Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Bobby P C
authors.initials: BP
authors.lastname: Koeleman
authors.affiliation: Department of Neurology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Kuhlenbäumer
authors.affiliation: Departments of Brain and Cognitive Sciences, Physiology and Cell Biology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Liron
authors.initials: L
authors.lastname: Sheintuch
authors.affiliation: Departments of Brain and Cognitive Sciences, Physiology and Cell Biology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ronel
authors.initials: R
authors.lastname: Veksler
authors.affiliation: Departments of Brain and Cognitive Sciences, Physiology and Cell Biology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Friedman
authors.affiliation: Tel Aviv University Medical School, Ramat Aviv, 69978, Israel.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Afawi
authors.affiliation: Department of Neuropediatrics, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.|Departments of Brain and Cognitive Sciences, Physiology and Cell Biology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
authors.forename: Ingo
authors.initials: I
authors.lastname: Helbig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004569:Electroencephalography; D017034:Epilepsy, Frontal Lobe / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007492:Iran; D007557:Israel; D007585:Jews / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D054220:Malformations of Cortical Development / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D000091042:Reelin Protein; D017422:Sequence Analysis, DNA; D012893:Sleep Wake Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human
keywords: Autosomal dominant epilepsy with auditory features; Autosomal dominant lateral temporal lobe epilepsy; Autosomal dominant partial epilepsy with auditory features; Epilepsies, partial [C10.228.140.490.360]; Genetic research [C10.228.140.490.360]; LGI1 protein, human [T329500]