3个 VHL 综合征家族的基因检测及临床调查

目的：明确 von Hippel-Lindau 综合征(VHL 综合征)家族基因突变及临床表现特点,筛查出家族内基因突变携带者行临床筛查,综合家族发病特点行家族健康指导。方法通过流行病学调查,共3例先证者临床诊断 VHL 综合征。抽取先证者及家族自愿者外周血,应用聚合酶链反应(PCR)体外扩增得到 vhl 基因片段,通过测序得到基因信息；再对家族内具有 vhl 基因突变的携带者进行头颅 MRI、腹部 B 超等对全身多系统行临床筛查；综合家族发病特点给出家族健康指导。结果3例先证者均发现 vhl 基因发生突变,家族1中5例成员基因阳性,突变方式为外显子1 c.330C > A；家族2先证者外显子3488delC；家族3发现7例基因阳性者,突变方式为外显子1 c.233G > A。其中,家族成员1III3、3III1、3III4、3IV3确定为基因突变携带者,临床检查显示其中3例成员已发病,1III3表现为双肾多发囊肿,胰腺多发囊肿；3III1表现为胰腺多发囊肿；3III4表现为视网膜血管母细胞瘤、胰腺多发囊肿,视网膜血管母细胞瘤接受激光治疗。3IV3由于年龄较小,临床检查未见明显异常。所有基因携带者接受规范化随访。结论基因检测可早期确诊 VHL 综合征,临床上对 vhl 基因突变患者需进行严密随访,从而提高患者治疗效果、延长生存期或改善生活质量。

Mutation analysis and clinical investigation of three Chinese families with VHL disease

Objective To detect the genetic mutations of vhl gene of three families who were diagnosed in clinical, and screen the carriers for clinical guiding treatment. Methods The vhl gene was screened for mutation using a di-rect DNA sequencing analysis for 31 members from three families. The genetic mutations carriers were required to undergo further clinical examination, surveillance and treatment. Results The genetic testing results were based on positive three probands. 5 members of family 1 had positive genes, 1 member in family 2, 7 members in family 3. The position of three von Hippel-Lindau syndrome(VHL) families genes mutations sites was separately on c. 330C > A in exon1, 488delC in exon3 and c. 233G > A in exon1. In DNA sequencing analysis, we found four po-tential carriers (1Ⅲ3, 3Ⅲ1, 3Ⅲ4, 3Ⅳ3),and combined with clinical examination, three(1Ⅲ3, 3Ⅲ1, 3Ⅳ3) of them had disease. 1Ⅲ3 was diagnosed with multi-cysts on kidney and pancreas, 3Ⅲ1 was diagnosed with pancreat-ic multi-cysts. 3Ⅲ4 was diagnosed with retinal hemangioblastoma. We had guided the member 3IV3 for eye surger-y. 3IV3 was not found with abnormal symptoms because of her young age. And all of the gene carriers should have the follow-up visit. Conclusion Genetic testing can diagnose VHL syndrome early. To improve patients'treatment, prolong survival and improve the quality of life,the patients with vhl gene mutations need follow-up closely.