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.
Pippucci, T., Licchetta, L., Baldassari, S., Palombo, F., Menghi, V., D'Aurizio, R., et al. (2015). Epilepsy with auditory features: A heterogeneous clinico-molecular disease. NEUROLOGY. GENETICS, 1(1), 1-8 [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 | |
---|---|---|---|
PIPPUCCI_2015_NEUROL GENET_EPILEPSY WITH AUDITORY FEATURES.pdf
accesso aperto
Tipo:
Versione (PDF) editoriale
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale - Non opere derivate (CCBYNCND)
Dimensione
492.39 kB
Formato
Adobe PDF
|
492.39 kB | Adobe PDF | Visualizza/Apri |
Additional Files.zip
accesso aperto
Tipo:
File Supplementare
Licenza:
Licenza per accesso libero gratuito
Dimensione
215.09 kB
Formato
Zip File
|
215.09 kB | Zip File | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.