Mutation information:
NumberExon/IntronNucleotide change Protein changeLocation Mutation typeConsequencesPhenotype InheritanceReference
147026c.4969C>Tp.Arg1657CysDIVS4MissenseP/﹢→N (180); G-LOFSMEIFamilial(Maternal,FS),P=4/4Lossin C.2003

Functional information:
NumberNucleotide changeProtein changeLocationPhenotypeFunctional defect type Details of the major biophysical abnormalities.Reference
41c.4969C>Tp.Arg1657Cys(R1657C)DIVS4SMEI fG-LOF Reduced current density and hypoexcitable (positive) shift of activation. Accelerated recovery from fast and slow inactivation.Lossin C. 2003

Inheritance information:
NumberNucleotide changeProtein changeMutation type Proband's phenotype1st transmitter's phenotype Mosaic Affected generationsPenetranceReference
142c.4969C>Tp.Arg1657Cys(DIVS4)MissenseSMEFS(Maternal) 4/4Lossin C.2003

[c.4969C>T] Clinical description

A ten-years-old boy was first seen at this institution at age 4.5 years. Family history was significant for benign childhood febrile seizures in the patient’s mother, maternal grandmother, and a maternal aunt. Gestation and birth were normal. He had  febrile convulsions at age two years and continued to have occasional simple febrile convulsions over the next few years, thereafter the patient occurred other seizures including myoclonic seizures with daily, spasms, absence seizures and GTCS with monthly. The spasms lasted a few seconds and consisted of eye elevation, trunk flexion, arm elevation with abduction and flexion at the elbows, and leg stiffening. These seizures were associated with altered awareness and responsiveness, and could be triggered by loud noises or bright lights. The medical and cutaneous were normal. Neurologic examination revealed difficulties with attention, concentration, and hyperactivity. He has had some behavioral problems at school with social interactions. Inpatient video-EEG monitoring performed at age four years and eight months demonstrated frequent interictal and ictal generalized spike or polyspike and slow wave discharges, multifocal independent epileptiform discharges, and mild generalized background slowing. The ictal discharges were associated with clinical myoclonic seizures. The MRI was normal. In this case, the patient’s phenotype could be considered moderately severe, while that of his affected relativeswas mild. R1657C mutation was originally described in a case of “extended spectrum of GEFS+”, but with spasms (early) and intractable and daily frequent myoclonic seizures(Grant AC, et al. Epilepsia. 2005;46 Suppl 10:39-40. [16359470]).