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, and SCN1A 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.
Epilepsy with auditory features: A heterogeneous clinico-molecular disease / 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.; Bisulli, F.. - In: NEUROLOGY. GENETICS. - ISSN 2376-7839. - ELETTRONICO. - 1:1(2015), pp. e5.1-e5.8. [10.1212/NXG.0000000000000005]
Epilepsy with auditory features: A heterogeneous clinico-molecular disease
PIPPUCCI, TOMMASO
;LICCHETTA, LAURA;Stipa, C.;SERI, MARCO;TINUPER, PAOLO;BISULLI, FRANCESCA
2015
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, and SCN1A 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.File | Dimensione | Formato | |
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