|Number||Exon/Intron||Nucleotide change||Protein change||Location||Mutation type||Consequences||Phenotype||Inheritance||Reference|
|1470||26||c.4969C>T||p.Arg1657Cys||DIVS4||Missense||P/﹢→N (180); G-LOF||SMEI||Familial(Maternal,FS),P=4/4||Lossin C.2003|
|Number||Nucleotide change||Protein change||Location||Phenotype||Functional defect type||Details of the major biophysical abnormalities.||Reference|
|41||c.4969C>T||p.Arg1657Cys(R1657C)||DIVS4||SMEI f||G-LOF||Reduced current density and hypoexcitable (positive) shift of activation. Accelerated recovery from fast and slow inactivation.||Lossin C. 2003|
|Number||Nucleotide change||Protein change||Mutation type||Proband's phenotype||1st transmitter's phenotype||Mosaic||Affected generations||Penetrance||Reference|
|[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. ).
Copyright ©2014 Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China
Collaborative Innovation Center for Neurogenetics and Channelopathies, Guangzhou 510260, China.