title: Complete loss of the cytoplasmic carboxyl terminus of the KCNQ2 potassium channel: a novel mutation in a large Czech pedigree with benign neonatal convulsions or other epileptic phenotypes.
abstract: OBJECTIVE
  Benign neonatal familial convulsions (BNFCs) represent a rare epileptic disorder with autosomal dominant mode of inheritance. To date, two voltage-gated potassium (K+) channel genes, KCNQ2 and KCNQ3, have been identified in typical BNFC families. The study of new pedigrees may help detect new mutations and define genotype-phenotype correlations.
  
  
  METHODS
  A large Czech family was detected in which BNFC was inherited together with a broad range of various nonneonatal epileptic phenotypes. Genetic linkage study and direct mutation analysis were performed to find the disease-causing mutation.
  
  
  RESULTS
  In seven patients with BNFCs and no recurrence of seizures, a novel two-base-pair deletion (1369del2) was identified within the coding sequence of the KCNQ2 gene. The mutation led to a putative protein that lacked nearly all its carboxyl terminus part, which plays a critical role for the accurate expression of the functional K+ channels. Three patients with generalized tonic-clonic seizures (GTCSs), all without any history of BNFCs, also displayed 1369del2. Three other patients with other idiopathic epileptic phenotypes did not have the mutation.
  
  
  CONCLUSIONS
  A novel 2-bp deletion within the coding sequence of the potassium channel KCNQ2 gene was detected in patients from a large and heterogeneous family with BNFCs or non-BNFC seizures.
authors.affiliation: INSERM U491, Marseille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pereira
authors.forename: Patrice
authors.initials: P
authors.lastname: Roll
authors.forename: Jitka
authors.initials: J
authors.lastname: Krizova
authors.forename: Pierre
authors.initials: P
authors.lastname: Genton
authors.forename: Milan
authors.initials: M
authors.lastname: Brazdil
authors.forename: Robert
authors.initials: R
authors.lastname: Kuba
authors.forename: Pierre
authors.initials: P
authors.lastname: Cau
authors.forename: Ivan
authors.initials: I
authors.lastname: Rektor
authors.forename: Pierre
authors.initials: P
authors.lastname: Szepetowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping / Q000379:methods; D003593:Cytoplasm / Q000235:genetics; D018153:Czech Republic; D004252:DNA Mutational Analysis; D020936:Epilepsy, Benign Neonatal / Q000235:genetics*; D005260:Female; D006801:Humans; D051658:KCNQ2 Potassium Channel; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D017384:Sequence Deletion
chemical_list: D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D010446:Peptide Fragments; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated