Benign familial neonatal convulsions caused by mutation in KCNQ3, exon 6: A European case

Fister, Petja; Soltirovska-Šalamon, Aneta; Debeljak, Maruša; Paro–Panjan, Darja

doi:10.1016/j.ejpn.2012.10.007

Cited by 13 publications

(15 citation statements)

References 8 publications

(8 reference statements)

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“…To date, six mutations of KCNQ3 have been reported in families with BFNE, one of them (p.Arg330Cys) being found in two families from different ethnic backgrounds [Charlier et al., ; Hirose et al., ; Singh et al., ; Li et al., ; Hahn and Neubauer, ; Fister et al., ; Zara et al, ]. All missense mutations and functional consequences have been studied for five of them; four of them (p.Glu299Lys, p.Asp305Gly, p.Trp309Arg, and p.Gly310Val) are located in the pore region of Q3 and the fifth one (p.Arg330Cys) immediately before S6.…”

Section: Discussionmentioning

confidence: 99%

NovelKCNQ2andKCNQ3Mutations in a Large Cohort of Families with Benign Neonatal Epilepsy: First Evidence for an Altered Channel Regulation by Syntaxin-1A

et al. 2014

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Mutations in the KCNQ2 and KCNQ3 genes encoding for K v 7.2 (KCNQ2; Q2) and K v 7.3 (KCNQ3; Q3) voltage-dependent K + channel subunits, respectively, cause neonatal epilepsies with wide phenotypic heterogeneity. In addition to benign familial neonatal epilepsy (BFNE), KCNQ2 mutations have been recently found in families with one or more family members with a severe outcome, including drug-resistant seizures with psychomotor retardation, electroencephalogram (EEG) suppression-burst pattern (Ohtahara syndrome), and distinct neuroradiological features, a condition that was named "KCNQ2 encephalopathy." In the present article, we describe clinical, genetic, and functional data from 17 patients/families whose electroclinical presentation was consistent with the diagnosis of BFNE. Sixteen different heterozygous mutations were found in KCNQ2, including 10 substitutions, three insertions/deletions and three large Additional Supporting Information may be found in the online version of this article. deletions. One substitution was found in KCNQ3.Most of these mutations were novel, except for four KCNQ2 substitutions that were shown to be recurrent. Electrophysiological studies in mammalian cells revealed that homomeric or heteromeric KCNQ2 and/or KCNQ3 channels carrying mutant subunits with newly found substitutions displayed reduced current densities. In addition, we describe, for the first time, that some mutations impair channel regulation by syntaxin-1A, highlighting a novel pathogenetic mechanism for KCNQ2-related epilepsies.

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Section: Discussionmentioning

confidence: 99%

NovelKCNQ2andKCNQ3Mutations in a Large Cohort of Families with Benign Neonatal Epilepsy: First Evidence for an Altered Channel Regulation by Syntaxin-1A

et al. 2014

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“…Several families have been reported with seizures that resolve before the age of 6 years without CVI or ID. [57][58][59][60][61][62][63][64][65] However, recently two additional families with seizures and variants in KCNQ3 have been reported in which family members had various IQ levels from severe ID to normal. 66,67 Therefore, the phenotypic spectrum of KCNQ3 variants appeared to be broader than benign epilepsy only and might well include CVI.…”

Section: Resultsmentioning

confidence: 99%

Novel genetic causes for cerebral visual impairment

et al. 2015

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“…3,9 To date, only nine missense KCNQ3 mutations have been reported in families with early onset epilepsies; seven in BFNS, 5,7,8,[10][11][12][13][14] and two in patients with seizure occurrence in the infantile age. 15,16 In most families with KCNQ3 mutations, affected members showed a benign disease course including age of onset and remission of seizures, sensitivity to AEDs, no recurrence of seizures after the neonatal-infantile period, and normal neurocognitive development.…”

Section: Discussionmentioning

confidence: 99%

“…A different KCNQ3 mutation at position 330 (R330C; Q3 R/C) has been described in families showing typical BFNS features including age of onset and remission of seizures, sensitivity to AEDs, no recurrence of seizures after the neonatal period, and normal neurocognitive development. 7,8 Heterologously expressed homomeric Q3 channels generated slowly activating voltage-dependent K + currents; by contrast, cells expressing Q3 R/L or R/C mutant subunits failed to generate detectable currents (Fig. 2B).…”

Section: Genetic and Functional Studiesmentioning

confidence: 99%

A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability

et al. 2014

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SUMMARYMutations in the KCNQ2 gene encoding for voltage-gated potassium channel subunits have been found in patients affected with early onset epilepsies with wide phenotypic heterogeneity, ranging from benign familial neonatal seizures (BFNS) to epileptic encephalopathy with cognitive impairment, drug resistance, and characteristic electroencephalography (EEG) and neuroradiologic features. By contrast, only few KCNQ3 mutations have been rarely described, mostly in patients with typical BFNS. We report clinical, genetic, and functional data from a family in which early onset epilepsy and neurocognitive deficits segregated with a novel mutation in KCNQ3 (c.989G>T; p.R330L). Electrophysiological studies in mammalian cells revealed that incorporation of KCNQ3 R330L mutant subunits impaired channel function, suggesting a pathogenetic role for such mutation. The degree of functional impairment of channels incorporating KCNQ3 R330L subunits was larger than that of channels carrying another KCNQ3 mutation affecting the same codon but leading to a different amino acid substitution (p.R330C), previously identified in two families with typical BFNS. These data suggest that mutations in KCNQ3, similarly to KCNQ2, can be found in patients with more severe phenotypes including intellectual disability, and that the degree of the functional impairment caused by mutations at position 330 in KCNQ3 may contribute to clinical disease severity.

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Benign familial neonatal convulsions caused by mutation in KCNQ3, exon 6: A European case

Cited by 13 publications

References 8 publications

NovelKCNQ2andKCNQ3Mutations in a Large Cohort of Families with Benign Neonatal Epilepsy: First Evidence for an Altered Channel Regulation by Syntaxin-1A

NovelKCNQ2andKCNQ3Mutations in a Large Cohort of Families with Benign Neonatal Epilepsy: First Evidence for an Altered Channel Regulation by Syntaxin-1A

Novel genetic causes for cerebral visual impairment

A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability

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