A novel mutation of KCNQ3 gene in a Chinese family with benign familial neonatal convulsions

Li, Haiyan; Li, Nan; Shen, Lu; Jiang, Hong; Yang, Qian; Song, Yue; Guo, Jifeng; Xia, Kun; Pan, Qian; Tang, Beisha

doi:10.1016/j.eplepsyres.2007.12.005

Cited by 22 publications

(23 citation statements)

References 20 publications

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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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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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“…Making the distinction accurately is of clinical significance as 15% of patients with KCNQ2 mutations have seizures in later life, while this is rare in patients with SCN2A mutations. Seizures in later life have also not been reported in patients with KCNQ3 mutations, although the total number of patients described with these mutations is small (Hirose et al, 2000;Singh et al, 2003;Li et al, 2008a). Genetic diagnosis therefore has prognostic value in these disorders in the context of predicting the likelihood of later seizures.…”

Section: Clinical Overlap Between Bfne and Bfniementioning

confidence: 99%

“…Only four mutations in KCNQ3 associated with BFNE have been reported in the literature. All of these affect amino acid residues located in or near the pore-loop Hirose et al, 2000;Singh et al, 2003;Li et al, 2008a). These mutations have not been functionally investigated, so their precise effect on channel function is unknown.…”

Section: Introductionmentioning

confidence: 99%

The Molecular Genetics of the Benign Epilepsies of Infancy

Heron¹,

Mulley²

2011

Clinical and Genetic Aspects of Epilepsy

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Clinical and Genetic Aspects of Epilepsy 96 overlaps with BFNE and BFIE. Seizure onset in BFNIE most commonly occurs at between 2 and 4 months of age. Clinically the condition was first described by Kaplan and Lacey (1983) and molecularly delineated two decades later (Heron et al., 2002). The aim of this chapter is to describe the current state of knowledge of the molecular genetics underlying these disorders and the significance that this has for patient care. The molecular genetics of benign familial neonatal epilepsyBenign familial neonatal epilepsy is most commonly caused by mutations in two related voltage-gated potassium channel subunit genes, KCNQ2 and KCNQ3. Together, these form the pore of the neuronal M-channel, which plays an important role in neuronal inhibition by acting as a "brake" on repetitive action potential discharges (Delmas & Brown, 2005). Mutations in KCNQ2 and KCNQ3 were originally described in 1998 (Biervert et al., 1998;Charlier et al., 1998;Singh et al., 1998). There are now more than 80 known mutations in KCNQ2; but only four described for KCNQ3. There may be other, rare, families with mutations in other genes. BFNE caused by mutations in the potassium channel subunit KCNQ2KCNQ2 (OMIM 602235) encodes one of the pore-forming subunits of the M-channel. The Mchannel is a heteromultimer consisting of two KCNQ2 and two KCNQ3 proteins, as well as accessory subunits. The gene is located close to the q-arm telomere of chromosome 20, at 20q13.3. It consists of 17 exons embedded within 87kb of genomic DNA. The gene codes for an 872 amino acid protein consisting of three domains: a short N-terminal domain; a transmembrane domain; and a large C-terminal domain, which contains regions that interact with other channel subunits. The gene has five splice variants, which produce proteins that differ in the C-terminal domains. The transmembrane domain consists of six transmembrane segments (S1-S6) and the pore-loop between segments S5 and S6, which forms the lining of the ion pore. The S4 domain is the voltage sensor and contains a number of positively charged arginine or lysine residues, which are required for normal channel function. The S4 segments move within the membrane in response to a change in voltage, opening the channel. BFNE was originally mapped to the KCNQ2 locus in 1989 (Leppert et al.) by linkage analysis of a large, four-generation pedigree. Further families were reported that confirmed the chromosome 20q localisation (Ryan et al., 1991;Malafosse et al., 1992). KCNQ2 was identified as the BFNE gene at this locus when a submicroscopic deletion containing KCNQ2 was detected in a single BFNE family. Screening of additional BFNE families revealed missense, frameshift and splice-site mutations in KCNQ2 . A frameshift mutation was simultaneously identified in KCNQ2 when it was screened as a candidate gene in another family mapped to the 20q locus (Biervert et al., 1998). In total, 85 mutations in KCNQ2 have been described in the scientific literature Soldovieri et al., 2007;Wuttke et al., 2...

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A novel mutation of KCNQ3 gene in a Chinese family with benign familial neonatal convulsions

Cited by 22 publications

References 20 publications

Novel genetic causes for cerebral visual impairment

Novel genetic causes for cerebral visual impairment

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

The Molecular Genetics of the Benign Epilepsies of Infancy

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