结节性硬化症患儿基因突变规律及其与临床表型关系

发布时间：2018-05-23 12:26

本文选题：结节性硬化症 + 儿童　；参考：《神经解剖学杂志》2017年02期

【摘要】：目的:检测结节性硬化症(TSC)患儿TSC1,TSC2基因突变类型,探讨其基因突变规律以及基因型与临床表型关系,为TSC分子遗传学研究提供资料。方法:收集2014~2016年徐州市儿童医院神经内科门诊及住院临床诊断为TSC患儿24例,提取血液标本的基因组DNA,二代基因测序技术(illumina/Solexa平台)进行检测。结果:(1)24例TSC患儿中23例检测到基因突变,突变率95.83%,其中TSC1基因突变4例(4/23,17.39%),TSC2基因突变19例(19/23,82.61%),新发突变18例(18/23,78.26%)。(2)TSC基因突变类型包括移码突变、错义突变、无义突变、剪切突变,大片段缺失,除2例患儿突变位点相同外,余均不相同。(3)TSC1基因突变患儿均为家族型,TSC2基因突变患儿5例为家族型(5/19,26.31%)。(4)癫痫发作类型TSC2基因突变患儿以痉挛发作为主(13/19,68.42%),TSC1基因突变患儿以局灶性发作为主(3/4,75.00%);癫痫3月完全控制率TSC2基因突变患儿为46.00%,TSC1基因突变患儿为75.00%,明显高于TSC2基因突变患儿(P0.01)。(5)TSC2基因突变患儿中智力发育落后(15/19,78.94%)明显多于TSC1基因突变患儿(1/4,25.00%,P0.01)。结论:TSC基因突变率较高,以TSC2为主,且无明显突变热点,新发突变多见。TSC1基因突变以家族型为主,TSC2基因突变以散发型为主。TSC2基因突变患儿临床表型相对TSC1基因突变患儿严重。
[Abstract]:Objective: to detect the mutation type of TSC1 and TSC2 gene in children with nodular sclerosis (TSC), explore the law of gene mutation and the relationship between genotypes and clinical phenotypes, and provide data for the study of TSC molecular genetics. Methods: 24 cases of TSC in the Department of Neurology in Xuzhou Children's Hospital and hospitalized in 2014~2016 were collected and the blood samples were extracted. Genomic DNA, two generation gene sequencing technology (illumina/Solexa platform) detection. Results: (1) 23 cases of 24 cases of TSC children detected gene mutation, the mutation rate was 95.83%, of which 4 cases of TSC1 mutation (4/23,17.39%), TSC2 gene mutation (19/23,82.61%), new mutation 18 cases (18/23,78.26%). (2) the type of TSC gene mutation, including the code shift mutation, error Mutation, nonsense mutation, shear mutation, large fragment deletion, except for the same mutation site in 2 cases, all of the children were family type, and 5 children with TSC2 gene mutation were family type (5/19,26.31%). (4) epileptic seizures type TSC2 mutations in children with spastic seizures mainly (13/19,68.42%), TSC1 gene mutations in children Focal seizures were mainly (3/4,75.00%); the total control rate of TSC2 gene mutation in children with total control in March was 46%, and that of children with TSC1 gene mutation was 75%, obviously higher than that of TSC2 mutation (P0.01). (5) the mental retardation (15/19,78.94%) in children with TSC2 gene mutation (15/19,78.94%) was more than that of TSC1 gene mutation (1/4,25.00%, P0.01). Conclusion: TSC gene The mutation rate was high, which was mainly TSC2, and there was no obvious mutation hot spot. The new mutation was mostly found in the family type.TSC1 gene mutation, and the TSC2 gene mutation in children with the main.TSC2 mutation was more serious than that of the TSC1 gene mutation in the children.
【作者单位】：徐州医科大学附属医院儿科;徐州市儿童医院神经内科;
【基金】：江苏省社会发展科技计划徐州市科技项目(KC14SH045)
【分类号】：R725.9

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