De novo FGF12 mutation in 2 patients with neonatal-onset epilepsy.

Autor:	Guella I; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Huh L; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., McKenzie MB; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Toyota EB; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Bebin EM; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Thompson ML; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Cooper GM; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Evans DM; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Buerki SE; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Adam S; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Van Allen MI; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Nelson TN; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Connolly MB; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Farrer MJ; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada., Demos M; Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada.
Jazyk:	angličtina
Zdroj:	Neurology. Genetics [Neurol Genet] 2016 Nov 10; Vol. 2 (6), pp. e120. Date of Electronic Publication: 2016 Nov 10 (Print Publication: 2016).
DOI:	10.1212/NXG.0000000000000120
Abstrakt:	Objective: We describe 2 additional patients with early-onset epilepsy with a de novo FGF12 mutation. Methods: Whole-exome sequencing was performed in 2 unrelated patients with early-onset epilepsy and their unaffected parents. Genetic variants were assessed by comparative trio analysis. Clinical evolution, EEG, and neuroimaging are described. The phenotype and response to treatment was reviewed and compared to affected siblings in the original report. Results: We identified the same FGF12 de novo mutation reported previously (c.G155A, p.R52H) in 2 additional patients with early-onset epilepsy. Similar to the original brothers described, both presented with tonic seizures in the first month of life. In the first patient, seizures responded to sodium channel blockers and her development was normal at 11 months. Patient 2 is a 15-year-old girl with treatment-resistant focal epilepsy, moderate intellectual disability, and autism. Carbamazepine (sodium channel blocker) was tried later in her course but not continued due to an allergic reaction. Conclusions: The identification of a recurrent de novo mutation in 2 additional unrelated probands with early-onset epilepsy supports the role of FGF12 p.R52H in disease pathogenesis. Affected carriers presented with similar early clinical phenotypes; however, this report expands the phenotype associated with this mutation which contrasts with the progressive course and early mortality of the siblings in the original report.
Databáze:	MEDLINE
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