CAJ | 학술논문

目的报告1个Ⅱ型神经纤维瘤病家系NF2基因的剪接突变(IVS3+3A＞C),并探讨基因型与表型的关系.方法先证者有听神经瘤家族史,2年前因听神经瘤已经伽玛刀治疗.提取该家系所有患者、疑似患者、正常成员和150个无血缘关系健康人的血样本基因组DNA.选择与NF2基因连锁的短串联重复(short tandem repeat,STR)位点(D22S1150、D22S268)对家系成员进行多态性分析,并计算2点连锁的LOD值.对先证者NF2基因的启动子、17个外显子和外显子内含子剪接处进行 PCR,对其产物进行测序.对家系另外3例患者,1例疑似患者和有血缘关系的9名健康者及150名无血缘的健康对照者进行第3外显子-第3内含子剪接处PCR和测序.结果两点连锁分析显示NF2基因为疾病的候选基因(Zmax=2.109,θ=0.00,D22S1150位点).PCR产物测序发现先证者NF2基因IVS3+3A＞C,呈杂合突变.3例患者和1例疑似患者均带有与先证者相同的突变,但9名健康成员和150名无血缘关系的健康对照者均无此改变.结论 NF2基因的INS3+3A＞C突变是该家系疾病的分子原因.
목적 보고1개Ⅱ형신경섬유류병가계NF2기인적전접돌변(IVS3+3A＞C),병탐토기인형여표형적관계.방법 선증자유은신경류가족사,2년전인은신경류이경가마도치료.제취해가계소유환자、의사환자、정상성원화150개무혈연관계건강인적혈양본기인조DNA.선택여NF2기인련쇄적단천련중복(short tandem repeat,STR)위점(D22S1150、D22S268)대가계성원진행다태성분석,병계산2점련쇄적LOD치.대선증자NF2기인적계동자、17개외현자화외현자내함자전접처진행 PCR,대기산물진행측서.대가계령외3례환자,1례의사환자화유혈연관계적9명건강자급150명무혈연적건강대조자진행제3외현자-제3내함자전접처PCR화측서.결과 량점련쇄분석현시NF2기인위질병적후선기인(Zmax=2.109,θ=0.00,D22S1150위점).PCR산물측서발현선증자NF2기인IVS3+3A＞C,정잡합돌변.3례환자화1례의사환자균대유여선증자상동적돌변,단9명건강성원화150명무혈연관계적건강대조자균무차개변.결론 NF2기인적INS3+3A＞C돌변시해가계질병적분자원인.
Objective To report a heterozygous RNA-splicing mutation (IVS3+3A＞C) of NF2 gene in a Chinese family with autosomal dominant neurofibromatosis type Ⅱ and investigate the relationship between the genotype and phenotype. Methods The proband with bilateral vestibular schwannomas undeiwent gamma knife radiosurgery two years earlier. DNA of blood samples from all affected individuals,suspected individuals and unaffected relatives of the family was extracted and amplified to detect the polymorphisms at loci D22S1150 and D22S268 that are linked with the NF2 gene. Two-point LOD score was calculated. The promoter region, 17 exons and exon/intron boundaries of NF2 gene were amplified and sequenced for the proband. The exon 3/intron 3 boundaries of NF2 gene was amplified and sequenced for the other 3 patients, 1 suspected individual, 9 unaffected members of the family and 150 unrelated controls.Results The result of two-point linkage analysis suggested that NF2 gene was a candidate gene (Zmax=2. 109, θ=0. 00, locus D22S1150). DNA sequencing revealed a heterozygous splicing mutation in intron 3 (IVS3+ 3A＞C) for the proband. Identical mutation was also observed in the other 3 patients and 1 suspected individual. No mutation was found in the 9 normal family members and 150 unrelated controls,which was consistent with the clinical diagnosis. Conclusion This is the first report of familial neurofibromatosis type Ⅱ with a splicing mutation of IVS3+3A＞C of the NF2 gene. The mutation might be responsible for the neurofibromatosis type Ⅱ in the family.