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

Autor:	Pippucci T; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., Licchetta L; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., Baldassari S; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., Palombo F; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., Menghi V; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., D'Aurizio R; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., Leta C; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., Stipa C; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., Boero G; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., d'Orsi G; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., Magi A; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., Scheffer I; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., Seri M; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., Tinuper P; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia., Bisulli F; U.O. Medical Genetics (T.P., M.S.), Polyclinic Sant'Orsola-Malpighi, Bologna, Italy; Department of Medical and Surgical Sciences (S.B., F.P., M.S.) and Department of Biomedical and Neuromotor Sciences (L.L., V.M., C.L., C.S., P.T., F.B.), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (L.L., V.M., C.L., C.S., P.T., F.B.), Bologna, Italy; Laboratory of Integrative Systems Medicine (LISM) (R.D'.A.), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council, Pisa, Italy; S.C. of Neurology (G.B.), SS. Annunziata Hospital, Taranto, Italy; Epilepsy Centre (G.d'.O.), Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy; Department of Clinical and Experimental Medicine (A.M.), University of Florence, Florence, Italy; and Florey Institute (I.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia.
Jazyk:	angličtina
Zdroj:	Neurology. Genetics [Neurol Genet] 2015 May 14; Vol. 1 (1), pp. e5. Date of Electronic Publication: 2015 May 14 (Print Publication: 2015).
DOI:	10.1212/NXG.0000000000000005
Abstrakt:	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.
Databáze:	MEDLINE
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