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中华诊断学电子杂志 ›› 2017, Vol. 05 ›› Issue (04) : 257 -262. doi: 10.3877/cma.j.issn.2095-655X.2017.04.010

所属专题: 文献

临床研究

Dravet综合征基因突变类型与临床表型的关系
罗甜1, 梁英武1,(), 高然1, 吕红艳1, 戚月凤1, 张延利1, 仇杰1   
  1. 1. 272013 济宁医学院附属济宁市第一人民医院儿科神经病区
  • 收稿日期:2017-07-23 出版日期:2017-11-26
  • 通信作者: 梁英武

The relationship between gene mutation types and clinical phenotypes in Dravet syndrome

Tian Luo1, Yingwu Liang1,(), Ran Gao1, Hongyan Lyu1, Yuefeng Qi1, Yanli Zhang1, Jie Qiu1   

  1. 1. Department of Pediatric Neurology, the first People’s Hospital Affiliated to Jining Medical University, Jining 272013, China
  • Received:2017-07-23 Published:2017-11-26
  • Corresponding author: Yingwu Liang
  • About author:
    Corresponding author: Liang Yingwu, Email:
引用本文:

罗甜, 梁英武, 高然, 吕红艳, 戚月凤, 张延利, 仇杰. Dravet综合征基因突变类型与临床表型的关系[J]. 中华诊断学电子杂志, 2017, 05(04): 257-262.

Tian Luo, Yingwu Liang, Ran Gao, Hongyan Lyu, Yuefeng Qi, Yanli Zhang, Jie Qiu. The relationship between gene mutation types and clinical phenotypes in Dravet syndrome[J]. Chinese Journal of Diagnostics(Electronic Edition), 2017, 05(04): 257-262.

目的

探讨Dravet综合征中不同基因突变类型与临床表型的关系。

方法

回顾性分析3例具有不同基因突变类型的Dravet综合征患儿的临床资料,分析典型及非典型Dravet综合征中临床表现和基因的遗传异质性,复习文献Dravet综合征不同基因突变类型及其相应的临床特征。

结果

病例1,有典型的Dravet综合征临床表现,如热敏感性、智力运动发育落后、发作时间逐渐延长,出现癫痫持续状态,对多种抗癫痫药耐药等,存在新发的钠离子通道α1亚基因(SCN1A)突变,该突变高度预示其致病性。病例2,有Dravet综合征的一些不典型特征,如无热惊厥、发作时间短暂,轻度智力运动发育落后,仅表现出语言、社交的落后,存在罕见的γ-氨基丁酸受体亚基因(GABRA6)突变。病例3,有CHD2基因突变中典型的肌阵挛表现,但尚未表现出失神发作、全面性强直发作以及癫痫持续状态,具有以构音障碍为主要表现的运动落后。

结论

除经典SCN1A以外其他不典型基因突变类型的Dravet综合征,其表型差异是非常普遍的,Dravet综合征定义应该为一个更广谱的系列。

Objective

To investigate the relationship between different types of gene mutations and clinical phenotypes in Dravet syndrome.

Methods

The clinical data of three patients with different types of gene mutations were analyzed retrospectively to illustrate the heterogeneity between gene mutation types and phenotypes in typical and atypical Dravet syndrome.Relevant literatures about the different types of gene mutations in Dravet syndrome and their corresponding clinical features were reviewed.

Results

The first patient suffered from a very typical manifestation of Dravet syndrome, such as heat sensitivity, mental retardation, the onset time gradually extended, epileptic status, resistance to a variety of antiepileptic drugs, with a new sodium channel α1 gene (SCN1A) mutation which indicated its pathogenicity.The second patient was with some atypical characteristics of Dravet syndrome, such as no febrile seizure, short episodes of attack, mild mental development only showing the language or social retardation.He carried a rare γ-aminobutyric acid receptor subunit (GABRA6) mutation.The third patient had CHD2 gene mutation with the typical myoclonus performance, but didn′t manifest the absence of seizure generalized tonic-clonic seizure and status epilepticus, with dysphonia as the main performance of the movement retardation.

Conclusion

The phenotypic differences of Dravet syndrome in typical mutations other than SCN1A is very common , and the definition of Dravet syndrome should be more broad spectrum series.

表1 3例Dravet综合征患儿的临床资料
图1 患儿及其亲属突变来源的等位基因特异性PCR测序峰图分析结果。检测基因为GABRA6,位置为chr:161116765。a、b图为患儿及其父亲PCR测序峰图,显示核苷酸变化为c.653A>C,为杂合突变;c、d图为患儿母亲及姐姐PCR测序峰图,无基因突变
[1]
Poryo M,Clasen O,Oehl-Jaschkowitz B, et al.Dravet syndrome:a new causative SCN1A mutation?[J]. Clin Case Rep, 2017, 5(5): 613-615.
[2]
Ozmen M,Dilber C,Tatl B, et al.Severe myoclonic epilepsy of infancy (Dravet syndrome):clinical and genetic features of nine Turkish patients[J]. Ann Indian Acad Neurol, 2011, 14(3): 178-181.
[3]
孙慧慧,张月华,徐小箐, 等. Dravet综合征SCN1A基因新生突变的来源研究[J]. 中华医学遗传学杂志, 2015, 32(4): 457-461.
[4]
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.
[5]
Kwong AK,Fung CW,Chan SY, et al.Identification of SCN1A and PCDH19 mutations in Chinese children with dravet syndrome[J]. PLoS One, 2012, 7(7): e41802.
[6]
Kang JQ,Macdonald RL, et al.GABRG2 Mutations Associated with a spectrum of epilepsy syndromes from generalized absence epilepsy to dravet syndrome[J]. JAMA Neurol, 2016, 73(8): 1009-1016.
[7]
Harkin LA,Bowser DN,Dibbens LM, et al.Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus[J]. Am J Hum Genet, 2002, 70(2): 530-536.
[8]
Patino GA,Claes LR,Lopez-Santiago LF, et al.A functional null mutation of SCN1B in a patient with Dravet syndrome[J]. J Neurosci, 2009, 29(34): 10764-10778.
[9]
Brackenbury WJ,Yuan Y,O'Malley HA, et al.Abnormal neuronal patterning occurs during early postnatal brain development of Scn1b-null mice and precedes hyperexcitability[J]. Proc Natl Acad Sci U S A, 2013, 110(3): 1089-1094.
[10]
Suls A,Jaehn JA,Kecskés A, et al.De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with dravet syndrome[J]. Am J Hum Genet, 2013, 93(5): 967-975.
[11]
Carvill GL,Weckhuysen S,McMahon JM, et al.GABRA1 and STXBP1:novel genetic causes of Dravet syndrome[J]. Neurology, 2014, 82(14): 1245-1253.
[12]
Baulac S,Gourfinkel-An I,Nabbout R, et al.Fever, genes, and epilepsy[J]. Lancet Neurol, 2004, 3(7): 421-430.
[13]
Sun H,Zhang Y,Liu X, et al.Analysis of SCN1A mutation and parental origin in patients with Dravet syndrome[J]. J Hum Genet, 2010, 55(7): 421-427.
[14]
Mulley JC,Scheffer IE,Petrou S, et al.SCN1A mutations and epilepsy[J]. Hum Mutat, 2005, 25(6): 535-542.
[15]
Xu X,Zhang Y,Sun H, et al.Early clinical features and diagnosis of Dravet syndrome in 138 Chinese patients with SCN1A mutations[J]. Brain Deiv, 2014, 36(8): 676-681.
[16]
Gontika MP,Konialis C,Pangalos C, et al.Novel SCN1A and GABRA1 gene mutations with diverse phenotypic features and the question on the existence of a broader spectrum of dravet syndrome[J]. Child Neurol Open, 2017(4): 2329048X17706794.
[17]
Olson HE,Poduri A,Pearl PL.Genetic forms of epilepsies and other paroxysmal disorders[J]. Semin Neurol, 2014, 34(3): 266-279.
[18]
Kodera H,Ohba C,Kato M, et al.De novo GABRA1 mutations in Ohtahara and West syndromes[J]. Epilepsia, 2016, 57(4): 566-573.
[19]
Thomas RH,Zhang LM,Carvill GL, et al.CHD2 myoclonic encephalopathy is frequently associated with self-induced seizures[J]. Neurology, 2015, 84(9): 951-958.
[20]
Guerrini R,Oguni H. Borderline Dravet syndrome:a useful diagnostic category?[J]. Epilepsia, 2011, 52(Suppl 2): 10-12.
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