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.

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Acknowledgments

We thank the family for participation in our study. We also thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about. The study was supported by the Deutsche Forschungsgemeinschaft with a Trilateral Grant (HE 5415/5-1) and within the EuroEPINOMICS project (HE 5415/3-1), the Christian-Albrechts-University Kiel and the Philipps-University Marburg.

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Correspondence to Karl Martin Klein.

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The study was approved by the local ethics committees of the participating sites and was therefore performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participants gave written informed consent prior to inclusion in the study.

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The authors declare that they have no conflict of interest.

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Klein, K.M., Pendziwiat, M., Cohen, R. et al. Autosomal dominant epilepsy with auditory features: a new LGI1 family including a phenocopy with cortical dysplasia. J Neurol 263, 11–16 (2016). https://doi.org/10.1007/s00415-015-7921-2

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Keywords

  • Epilepsies, partial [C10.228.140.490.360]
  • Genetic research [C10.228.140.490.360]
  • LGI1 protein, human [T329500]
  • Autosomal dominant epilepsy with auditory features
  • Autosomal dominant partial epilepsy with auditory features
  • Autosomal dominant lateral temporal lobe epilepsy