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Epilepsy with auditory features: A heterogeneous clinico-molecular 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, 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.

SUBMITTER: Pippucci T

PROVIDER: S-EPMC4821078 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Epilepsy with auditory features: A heterogeneous clinico-molecular disease.

Pippucci Tommaso T Licchetta Laura L Baldassari Sara S Palombo Flavia F Menghi Veronica V D'Aurizio Romina R Leta Chiara C Stipa Carlotta C Boero Giovanni G d'Orsi Giuseppe G Magi Alberto A Scheffer Ingrid I Seri Marco M Tinuper Paolo P Bisulli Francesca F

Neurology. Genetics 20150514 1

<h4>Objective</h4>To identify novel genes implicated in epilepsy with auditory features (EAF) in phenotypically heterogeneous families with unknown molecular basis.<h4>Methods</h4>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, s ...[more]

PMID: 27066544

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Dataset Information

Epilepsy with auditory features: A heterogeneous clinico-molecular disease.

Publications

Epilepsy with auditory features: A heterogeneous clinico-molecular disease.

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