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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(P<0.01)。(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%,P<0.01)。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。
Objective: To detect the types of TSC1 and TSC2 gene mutations in children with tuberous sclerosis (TSC), investigate their gene mutation patterns and the relationships between genotypes and clinical phenotypes and provide information for molecular genetics studies of TSC. Methods: The clinical data of 24 outpatients and inpatients with TSC were collected from Department of Neurology, Children’s Hospital of Xuzhou from 2014 to 2016. The genomic DNA was extracted from the blood samples and the second generation gene sequencing technology (Illumina / Solexa platform) was used to detect. Results: (1) Twenty-four cases of TSC detected gene mutations, the mutation rate was 95.83%, including TSC1 gene mutation in 4 cases (4 / 23,17.39%), TSC2 gene mutation in 19 cases (19 / 23,82.61% ), New mutations in 18 cases (18 / 23,78.26%). (2) TSC gene mutation types include frameshift mutation, missense mutation, nonsense mutation, shearing mutation and large fragment deletion, except for the same mutation sites in 2 cases. (3) All children with TSC1 gene mutation were familial and 5 children with TSC2 gene mutation were familial (5/19, 26.31%). (4) Epileptic seizure type TSC2 gene mutation mainly occurred in children with spasm (13 / 19,68.42%). TSC1 gene mutation mainly occurred in children with focal seizure (3/4, 75.00%); epilepsy was completed in March Control rate of TSC2 gene mutation in children was 46.00%, TSC1 gene mutation in children was 75.00%, was significantly higher than TSC2 gene mutation in children (P <0.01). (5) Children with TSC2 gene mutation lagged significantly (15 / 19,78.94%) than children with TSC1 mutation (1 / 4,25.00%, P <0.01). CONCLUSIONS: The mutation rate of TSC gene is high, mainly TSC2, and no obvious mutation hot spots, new mutations are more common. The TSC1 gene mutation is mainly familial and the TSC2 gene mutation is predominately sporadic. TSC2 mutations in children with clinical phenotype relative TSC1 gene mutation in children with severe.