CAJ | 학술논문

目的对结节性硬化症(tuberous sclerosis complex,TSC)患者进行基因突变检测,并在基因诊断结果明确的基础上应用于产前诊断.方法应用聚合酶链反应-变性高效液相色谱(polymerase chain reaction-denaturing high-performance liquid chromatography,PCR-DHPLC)、DNA测序技术,对19个家系的21例TSC患者进行TSC1和TSC2基因的突变检测.结果在19个家系21例患者中发现17种不同的基因突变,其中13种突变未见报道,包括TSCj基因的c.2672delA、c.2672insA和TSC2基因的c.4918insCGCC、c.1143delG、Intron27+1 G＞A、c.1957-1958delAG、Intron5+1 G＞A、c.910insCT、c.2753C＞G、c.4078dupAGCAAGTCCAGCTCCTC、Intron 11-1 G＞A、Intron 14+1 G＞A、c.684 C＞A.对7个家系进行了产前诊断,其中6个家系的胎儿均未发现其家系先证者所具有的突变,胎儿出生后电话随访至1～4岁无TSC的症状出现.而另一家系的胎儿携带有和母亲一样的突变,经遗传咨询后,家属选择了引产.结论本研究证实的TSC基因突变中,有76.5%(13/17)的突变均未在其他研究中被发现,说明中国人群TSC基因的突变谱可能与其他人群具有较明显的差异;本研究中TSC基因诊断率为89.5%(17/19),提示TSC的发生可能还有其它未知的遗传病因;在有家族史的病例中,TSC1与TSC2有相似的突变比例,而在散发病例中,TSC2的突变更加常见;13种新突变患者的父母均无类似突变,说明TSC致病基因具有较高的自发突变率.
목적 대결절성경화증(tuberous sclerosis complex,TSC)환자진행기인돌변검측,병재기인진단결과명학적기출상응용우산전진단.방법 응용취합매련반응-변성고효액상색보(polymerase chain reaction-denaturing high-performance liquid chromatography,PCR-DHPLC)、DNA측서기술,대19개가계적21례TSC환자진행TSC1화TSC2기인적돌변검측.결과 재19개가계21례환자중발현17충불동적기인돌변,기중13충돌변미견보도,포괄TSCj기인적c.2672delA、c.2672insA화TSC2기인적c.4918insCGCC、c.1143delG、Intron27+1 G＞A、c.1957-1958delAG、Intron5+1 G＞A、c.910insCT、c.2753C＞G、c.4078dupAGCAAGTCCAGCTCCTC、Intron 11-1 G＞A、Intron 14+1 G＞A、c.684 C＞A.대7개가계진행료산전진단,기중6개가계적태인균미발현기가계선증자소구유적돌변,태인출생후전화수방지1～4세무TSC적증상출현.이령일가계적태인휴대유화모친일양적돌변,경유전자순후,가속선택료인산.결론 본연구증실적TSC기인돌변중,유76.5%(13/17)적돌변균미재기타연구중피발현,설명중국인군TSC기인적돌변보가능여기타인군구유교명현적차이;본연구중TSC기인진단솔위89.5%(17/19),제시TSC적발생가능환유기타미지적유전병인;재유가족사적병례중,TSC1여TSC2유상사적돌변비례,이재산발병례중,TSC2적돌변경가상견;13충신돌변환자적부모균무유사돌변,설명TSC치병기인구유교고적자발돌변솔.
Objective To screen mutations of tuberous sclerosis complex (TSC) patients to confirm a clinical diagnosis of TSC, and to perform prenatal diagnosis for families with mutations. Methods In this study, PCR-denaturing high-performance liquid chromatography(DHPLC), supplemented with sequencing when necessary, was used to screen TSC1 and TSC2 mutations in 21 patients from 19 pedigrees visited author's hospital in the last five years. For novel mutations, one hundred unrelated healthy individuals were screened to exclude the possibility of polymorphism. Results Seventeen different mutations were found in 21 patients of 19 pedigrees with 13 being novel mutations, including c. 2672delA, c. 2672insA of TSC1gene and c. 4918insCGCC, c. 1143delG, Intron27 + 1 G＞ A, c. 1957-1958delAG, Intron5 + 1 G＞ A,c. 910insCT, c. 2753 C＞G, c. 4078dupAGCAAGTCCAGCTCCTC, Intron 11 -1 G＞A, Intron 14 +1 G＞A, c. 684 C＞A of TSC2 gene, indicating a high frequency of de novo mutations in TSC. Three of these mutations were in the TSC1 gene (N762S, c. 2672insA and c. 2672delA), while all remaining 14 were in the TSC2 gene. Prenatal diagnosis for TSC was performed for 7 fetuses from these pedigrees. The six fetuses that tested negative for TSC mutations were carried to term and, to date, none of these children has shown symptoms of TSC. Conclusion Author's data showed that a mutation detection rate of tuberous sclerosis was 89.5%(17/19) among patients in author's hospital. The ratio of TSC2 and TSC1 mutations was about 1 : 1 in the familial cases, but TSC2 mutation was more common than TSC1 mutation in sporadic cases.Author's data demonstrated that birth of TSC children for those with familial history of TSC could be prevented through prenatal diagnosis.