Abstract Objective To investigate the characteristics of gene mutations in unexplained infantile epileptic encephalopathy (EE).Methods A total of 47 infants with unexplained infantile EE were enrolled, and next-generation sequencing was used to analyze gene mutations in these infants and their parents.Results Of all 47 infants, 23 were found to have gene mutations, among whom 13 had de novo mutations and 10 had heterozygous mutations inherited from their father or mother. Among the 23 infants with gene mutations, 17 were found to have the gene mutations related to EE (among whom 14 had ion channel gene mutations), 2 had the gene mutations related to congenital inherited metabolic diseases, 2 had the gene mutations related to brain structural abnormality, and 2 had the gene mutations related to mental retardation.Conclusions Unexplained infantile EE may have gene mutations, mainly ion channel gene mutations.
Engel J Jr, International League Against Epilepsy (ILAE). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy:report of the ILAE task force on classification and terminology[J]. Epilepsia, 2001, 42(6):796-803.
[2]
Hildebrand MS, Dahl HH, Damiano JA, et al. Recent advances in the molecular genetics of epilepsy[J]. J Med Genet, 2013, 50(5):271-279.
[3]
Thomas RH, Berkovic SF. The hidden genetics of epilepsy-a clinically important new paradigm[J]. Nat Rev Neurol, 2014, 10(5):283-292.
[4]
Nordli DR Jr. Epileptic encephalopathies in infants and children[J]. J Clin Neurophysiol, 2012, 29(5):420-424.
[5]
Helbig I, Tayoun AA. Understanding genotypes and phenotypes in epileptic encephalopathies[J]. Mol Syndromol, 2016, 7(4):172-181.
Kong W, Zhang Y, Gao Y, et al. SCN8A mutations in Chinese children with early onset epilepsy and intellectual disibilities[J]. Epilepsia, 2015, 56(3):431-438.
Martin HC, Kim GE, Pagnamenta AT, et al. Clinical whole-genome sequenceing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis[J]. Hum Mol Genet, 2014, 23(12):3200-3211.
Zhang Q, Li J, Zhao Y, et al. Gene mutation analysis of 175 Chinese patients with early-onset epileptic encephalopathy[J]. Clin Genet, 2017, 91(5):717-724.
[12]
Gokben S, Onay H, Yilmaz S, et al. Targeted next generation sequencing:the diagnostic value in early-onset epileptic encephalopathy[J]. Acta Neurol Belg, 2017, 117(1):131-138.
[13]
Dravet C. The core Dravet syndrome phenotype[J]. Epilepsia, 2011, 52(Suppl 2):3-9.
[14]
Depienne C, Bouteiller D, Keren B, et al. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females[J]. PLoS Genet, 2009, 5(2):e1000381.
[15]
Gataullina S, Dulac O. From genotype to phenotype in Dravet disease[J]. Seizure, 2017, 44:58-64.
[16]
Wang Y, Du X, Bin R, et al. Genetic variants identified from epilepsy of unknown etiology in Chinese children by targeted exome sequencing[J]. Sci Rep, 2017, 7:40319.
[17]
Epi4K and EPGP Investigators. De novo mutations in the classic epileptic encephalopathies[J]. Nature, 2013, 501(7466):217-221.
[18]
Kodera H, Nakamura K, Osaka H, et al. De novo mutations in SLC35A2 encoding a UDP-galactose transporter cause early-onset epileptic encephalopathy[J]. Hum Mutat, 2013, 34(12):1708-1714.
[19]
Leuzzi V, Mastrangelo M, Battini R, et al. Inborn errors of creatine metabolism and epilepsy[J]. Epilepsia, 2013, 54(2):217-227.
[20]
Berryer MH, Hamdan FF, Klitten LL, et al. Mutations in SYNGAP1 cause intellectual disability, autism and a specific form of epilepsy by inducing haploinsufficiency[J]. Hum Mutat, 2013, 34(2):385-394.
[21]
Carvill GL, Heavin SB, Yendle SC, et al. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1[J]. Nat Genet, 2013, 45(7):825-830.
[22]
Van Maldergem L, Hou Q, Kalscheuer VM, et al. Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism sepectrum disorder and impairs neurite outgrowth[J]. Hum Mol Genet, 2013, 22(16):3306-3314.
[23]
de Lange IM, Helbig KL, Weckhuysen S, et al. De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy[J]. J Med Genet, 2016, 53(12):850-858.
