Whole Exome Sequencing And Its Significance Of Idiopathic Generalized Epilepsy With Generalized Tonic-clonic Seizures Only Patients

Objective:Genes of patients with Idiopathic generalized epilepsy with generalized tonic-clonic seizures only(IGTCS)were sequenced by the whole exome sequencing to explore the pathogenic gene and pathogenesis of IGTCS from the gene level,in order to provide the theoretical basis for individual treatment of IGTCS patients.Methods:From June 2015 to December 2016,83 patients were selected with IGTCS at the Department of Neurology,Xijing Hospital,Fourth Military Medical University,China.The genes of these patients were sequenced by the whole exome sequencing.The result was compared with normal genome in NCBI database and the gene mutations were found in the human genome database.The biological information technology was adopted to predict the mutation sites and its effect on protein function.Results:There were 83 patients diagnosed with IGTCS from June 2015 to December 2016 at the Department of Neurology,Xijing Hospital,whose genes were sequenced by the whole exome sequencing.There were 42 males and 41 females at the age of 3~31 years old,witha medical history of 1~23 years among them.The results showed that 70 cases were positive in all of the 83 patients,and 13 cases were negative.In the 70 positive patients,the frequency of gene mutation from high to low was CACNA1H(n=17),GPR98(n=16),SCN9A(n=12),CASR(n=7),and GRIN2A(n=5).1.There are genetic mutations in CACNA1 H,c.844G>A,c.2243C>T and c.2318G>A,that exist in IGTCS patients.The three mutations has been confirmed related to CAE in the past research.Four mutations that hasn’t reported,c.489G>C,c.568G>A,c.884G>A and c.4045G>A,were found at the same time.Amino acids Gln at the position163,Gly at the position 190,Arg at the position 295 and Ala at the position 1349 coded by them are in the highly conservative region in the process of biological evolution.And PolyPhen methods were adopted to predict that these amino acids could affect their protein function.2.A novel genetic mutation c.1797A>T in GPR98 was found in IGTCS patients,amino acid Arg at the position 599 coded by which is in the highly conservative region in the process of biological evolution.And PolyPhen methods were adopted to predict that this amino acid could affect its protein function.3.In IGTCS patients,genetic mutations c.2089C>T,c.2132T>C and c.2359T>C in SCN9 A haven’t reported before and amino acid Gln at the position 697,Leu at the position 711 and Met at the position 787 coded by them are in the highly conservative region in the process of biological evolution.And PolyPhen and SIFT methods were adopted to predict that these amino acids could affect their protein function.4.In IGTCS patients,genetic mutation c.1316C>G in CASR hasn’t reported before and amino acid Pro at the position 439 coded by which is in the highly conservative region in the process of biological evolution.And PolyPhen methods were adopted to predict that this amino acid could affect its protein function.5.In IGTCS patients,genetic mutation c.2627T>C in GRIN2 A hasn’t reported before and amino acid Ile at the position 876 coded by which is in the highly conservative region in the process of biological evolution.And PolyPhen methods were adopted to predict that this amino acid could affect its protein function.Conclusions:1.Gene mutations of CACNA1 H,GPR98,SCN9 A,CASR and GRIN2 A may be associated with IGTCS.2.Patients with IGTCS and CAE may have common susceptibility genes.3.Susceptibility genes related to CAE in previous studies may also be found in other types of IGE.