TY - JOUR
T1 - Autosomal recessive cortical myoclonic tremor and epilepsy
T2 - Association with a mutation in the potassium channel associated gene CNTN2
AU - Stogmann, Elisabeth
AU - Reinthaler, Eva
AU - Eltawil, Salwa
AU - El Etribi, Mohammed A.
AU - Hemeda, Mahmoud
AU - El Nahhas, Nevine
AU - Gaber, Ahmed M.
AU - Fouad, Amal
AU - Edris, Sherif
AU - Benet-Pages, Anna
AU - Eck, Sebastian H.
AU - Pataraia, Ekaterina
AU - Mei, Davide
AU - Brice, Alexis
AU - Lesage, Suzanne
AU - Guerrini, Renzo
AU - Zimprich, Friedrich
AU - Strom, Tim M.
AU - Zimprich, Alexander
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - CNTN2
KW - cortical myoclonic tremor and epilepsy
KW - whole-exome sequencing
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U2 - 10.1093/brain/awt068
DO - 10.1093/brain/awt068
M3 - Article
C2 - 23518707
AN - SCOPUS:84876064861
VL - 136
SP - 1155
EP - 1160
JO - Brain
JF - Brain
SN - 0006-8950
IS - 4
ER -