SCN1A mutation database!

Mutation information:

Number	Exon/Intron	Nucleotide change	Protein change	Location	Mutation type	Consequences	Phenotype	Inheritance	Reference
659	14	c.2576G>A	p.Arg859His	DIIS4	Missense	P/﹢→P/﹢(29); G-LOF	GEFS+	NA	Volkers L.2011
							PEFS+	Familial(Paternal,GEFS+),P=2/2	Volkers L.2011
							Epilepsy and/or NDD	NA	Lindy AS.2018
							FS+ with absence	Paternal grandfather posttraumatic sz，Maternal grandfather sz with brain tumor	Myers KA.2017

Functional information:

Number	Nucleotide change	Protein change	Location	Phenotype	Functional defect type	Details of the major biophysical abnormalities.	Reference
13	c.2576G>A	p.Arg859His(R859H)	DIIS4	PEFS+ ^f	G-LOF	Increased 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:

Number	Nucleotide change	Protein change	Mutation type	Proband's phenotype	1st transmitter's phenotype	Mosaic	Affected generations	Penetrance	Reference
72	c.2576G>A	p.Arg859His(DIIS4)	Missense	PEFS+	GEFS+(Paternal)		2	2/2	Volkers 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]).

[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]).

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.