Autosomal recessive cortical myoclonic tremor and epilepsy: Association with a mutation in the potassium channel associated gene CNTN2

Elisabeth Stogmann, Eva Reinthaler, Salwa Eltawil, Mohammed A. El Etribi, Mahmoud Hemeda, Nevine El Nahhas, Ahmed M. Gaber, Amal Fouad, Sherif Edris, Anna Benet-Pages, Sebastian H. Eck, Ekaterina Pataraia, Davide Mei, Alexis Brice, Suzanne Lesage, Renzo Guerrini, Friedrich Zimprich, Tim M. Strom, Alexander Zimprich

Research output: Contribution to journalArticlepeer-review


We characterize a consanguineous Egyptian family with an autosomal recessively inherited familial cortical myoclonic tremor and epilepsy. We used multipoint linkage analysis to map the causative mutation to a 12.7 megabase interval within 1q31.3-q32.2 with a log of odds score of 3.6. For further investigation of the linked region in an efficient and unbiased manner, we performed exome sequencing. Within the suspected region we identified a homozygous single base pair deletion (c.503-503delG) leading to a frameshift in the coding region of the sixth exon of CNTN2 alias TAG-1 (p.Trp168fs), which segregated in the respective family. Many studies point towards an important role of the CNTN2 product contactin 2 in neuronal excitability. Contactin 2, a glycosylphosphatidylinositol-anchored neuronal membrane protein, and another transmembrane protein called contactin associated protein-like 2 (CNTNAP2 alias CASPR2) are together necessary to maintain voltage-gated potassium channels at the juxtaparanodal region. CNTN2 knockout mice were previously reported to suffer from spontaneous seizures and mutations in the CNTNAP2 gene have been described to cause epilepsy in humans. To further delineate the role of CNTN2 in patients with epilepsy, we sequenced the coding exons in 189 Caucasian patients with epilepsy. No recessive mutation was detected and heterozygote carriers of rare CNTN2 variants do not seem to be predisposed to epilepsy. Given the severity of the mutation and the proposed function of the gene, we consider this mutation as the most likely cause for cortical myoclonic tremor and epilepsy in this family.

Original languageEnglish
Pages (from-to)1155-1160
Number of pages6
Issue number4
Publication statusPublished - 2013


  • CNTN2
  • cortical myoclonic tremor and epilepsy
  • whole-exome sequencing

ASJC Scopus subject areas

  • Clinical Neurology


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