Mutation information:
NumberExon/IntronNucleotide change Protein changeLocation Mutation typeConsequencesPhenotype InheritanceReference
65914c.2576G>Ap.Arg859HisDIIS4MissenseP/﹢→P/﹢(29); G-LOF GEFS+NAVolkers L.2011
PEFS+ Familial(Paternal,GEFS+),P=2/2Volkers L.2011
Epilepsy and/or NDDNALindy AS.2018
FS+ with absencePaternal grandfather posttraumatic sz,Maternal grandfather sz with brain tumorMyers KA.2017

Functional information:
NumberNucleotide changeProtein changeLocationPhenotypeFunctional defect type Details of the major biophysical abnormalities.Reference
13c.2576G>Ap.Arg859His(R859H)DIIS4PEFS+ fG-LOFIncreased persistent current and slower inactivation rate constant; reduction in voltage dependent steady state channel availability and a delayed recovery from fast inactivation.Volkers L.2011

Inheritance information:
NumberNucleotide changeProtein changeMutation type Proband's phenotype1st transmitter's phenotype Mosaic Affected generationsPenetranceReference
72c.2576G>Ap.Arg859His(DIIS4)MissensePEFS+GEFS+(Paternal) 22/2Volkers L.2011

[c.2576G>A] Clinical description

The novel R859H mutation was detected in a girl diagnosed with GEFS+ and a paternal history of (a)febrile seizures. Her febrile convulsions, generalized tonic-clonic seizures, started at the age of 13 months after a Diphtheria/Tetanus/whole cell Pertussis/inactivated poliovirus (DTwcP-IPV) and Haemophilus influenzae type b (Hib) vaccination and were recurrent and often prolonged. After the age of 3.5 years she also experienced afebrile GTCS and an isolated complex partial seizure. Electroencephalography demonstrated bilateral occipital-temporal spike-wave complexes and a few predominantly left-sided isolated occipital spike-waves. The patient responded well to valproate. Her last seizure was reported at age 5.5 years and EEG analysis at the age of 6 years did not show epileptiform activity. She had normal development except for some features of attention deficit hyperactivity disorder. Her father experienced approximately ten febrile seizures between age one and six years. In the next nine years, he experienced approximately five afebrile seizures. He received valproate from age 11 years until he was 17 years old. The family history of first-degree relatives was negative for febrile or afebrile seizures(Volkers L,et al. Eur J Neurosci. 2011 Oct;34(8): 1268-75. [21864321]).