1. Epilepsy with auditory features
- Author
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Francesca Bisulli, Paolo Tinuper, Tommaso Pippucci, Marco Seri, G. Boero, Carlotta Stipa, Laura Licchetta, Alberto Magi, Chiara Leta, Ingrid E. Scheffer, Sara Baldassari, Veronica Menghi, Giuseppe d'Orsi, Romina D'Aurizio, Flavia Palombo, Pippucci, T., Licchetta, L., Baldassari, S., Palombo, F., Menghi, V., D'Aurizio, R., Leta, C., Stipa, C., Boero, G., D'Orsi, G., Magi, A., Scheffer, I., Seri, M., Tinuper, P., and Bisulli, F.
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Proband ,CNTNAP2 ,epilepsy with auditory feature ,Biology ,medicine.disease_cause ,Article ,Genetics ,medicine ,Missense mutation ,Copy-number variation ,Genetics (clinical) ,Mutation ,EAF ,DEPDC5 ,Phenotype ,3. Good health ,CNV, epilepsy with auditory features ,Potassium channel complex ,LGI1 ,Neurology (clinical) ,Neurology disease - Abstract
Objective: To identify novel genes implicated in epilepsy with auditory features (EAF) in phenotypically heterogeneous families with unknown molecular basis. Methods: We identified 15 probands with EAF in whom an LGI1 mutation had been excluded. We performed electroclinical phenotyping on all probands and available affected relatives. We used whole-exome sequencing (WES) in 20 individuals with EAF (including all the probands and 5 relatives) to identify single nucleotide variants, small insertions/deletions, and copy number variants. Results: WES revealed likely pathogenic variants in genes that had not been previously associated with EAF: a CNTNAP2 intragenic deletion, 2 truncating mutations of DEPDC5, and a missense SCN1A change. Conclusions: EAF is a clinically and molecularly heterogeneous disease. The association of EAF with CNTNAP2, DEPDC5 ,a ndSCN1A mutations widens the phenotypic spectrum related to these genes. CNTNAP2 encodes CASPR2, a member of the voltage-gated potassium channel complex in which LGI1 plays a role. The finding of a CNTNAP2 deletion emphasizes the importance of this complex in EAF and shows biological convergence. Neurol Genet 2015;1:e5; doi
- Published
- 2015
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