Abstract
Mutations 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.
| Original language | English |
|---|---|
| Pages (from-to) | e15-e20 |
| Journal | Epilepsia |
| Volume | 56 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2015 |
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Keywords
- Benign familial neonatal seizures
- Cognitive impairment
- Epilepsy
- Genotype-phenotype correlations
- KCNQ
- Mutagenesis
- Voltage-gated potassium channels
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
- Medicine(all)
Cite this
A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability. / Miceli, Francesco; Striano, Pasquale; Soldovieri, Maria Virginia; Fontana, Antonina; Nardello, Rosaria; Robbiano, Angela; Bellini, Giulia; Elia, Maurizio; Zara, Federico; Taglialatela, Maurizio; Mangano, Salvatore.
In: Epilepsia, Vol. 56, No. 2, 01.02.2015, p. e15-e20.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability
AU - Miceli, Francesco
AU - Striano, Pasquale
AU - Soldovieri, Maria Virginia
AU - Fontana, Antonina
AU - Nardello, Rosaria
AU - Robbiano, Angela
AU - Bellini, Giulia
AU - Elia, Maurizio
AU - Zara, Federico
AU - Taglialatela, Maurizio
AU - Mangano, Salvatore
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Mutations 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.
AB - Mutations 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.
KW - Benign familial neonatal seizures
KW - Cognitive impairment
KW - Epilepsy
KW - Genotype-phenotype correlations
KW - KCNQ
KW - Mutagenesis
KW - Voltage-gated potassium channels
UR - http://www.scopus.com/inward/record.url?scp=84923359250&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923359250&partnerID=8YFLogxK
U2 - 10.1111/epi.12887
DO - 10.1111/epi.12887
M3 - Article
C2 - 25524373
AN - SCOPUS:84923359250
VL - 56
SP - e15-e20
JO - Epilepsia
JF - Epilepsia
SN - 0013-9580
IS - 2
ER -