摘要目的 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.

abstractsObjective 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.