摘要
目的 探讨中国人一个 von Hippel- L indau(VHL)病家系的临床特点及基因突变研究的临床意义。方法 调查一个 von Hippel- L indau病大家系 ,制定该家系发病的树状图 ;抽取 2 7位家族成员外周血 ,采用聚合酶链反应和扩增产物直接测序进行基因检测 ;通过病史和影像学检查 ,获得该病的多脏器肿瘤发生情况。结果 该家族 4代 4 7人中 18人患 von Hippel- L indau病 ,其中中枢神经系统成血管细胞瘤 5例 ,肾癌合并中枢神经系统成血管细胞瘤 3例 ,肾癌合并视网膜血管瘤 3例 ,肾癌合并胰腺多发性囊肿 1例 ,肾癌合并视网膜血管瘤及胰腺多发性囊肿 2例 ,肾癌合并中枢神经系统成血管细胞瘤及胰腺多发性囊肿 1例 ,肾脏多发性囊肿合并胰腺多发性囊肿 1例和胰腺多发性囊肿 2例。本组中 ,肾癌、中枢神经系统成血管细胞瘤、视网膜血管瘤和胰腺多发性囊肿的发生率分别为 5 6 %、5 0 %、2 8%和 39%。基因检测发现 VHL 基因第 1外显子上第 4 4 6位核苷酸 A→ G突变 ,该突变导致第 78位编码氨基酸由天冬酰胺转变为丝氨酸。检测的 2 7人中 ,15人呈现 VH L基因突变 ,其中 9例患病者、4例致病基因携带者及 2例经影象学检查外科手术证实的无症状患者。其余 12人无基因突变 ,同时无相应临床征象。结论 该家系属于 von Hippel-
ObjectiveTo report the clinical characterization of a large Chinese kindred with von Hippel-Lindau (VHL) disease and to evaluate the role of VHL genetic testing in diagnosis of VHL disease and clinical screening for members in VHL disease family. MethodsA large kindred with VHL disease was studied. DNA extracted from peripheral blood was amplified by PCR to three exons of VHL gene in 27 members. PCR products were directly sequenced. The data on involvement of multi-organs in the VHL disease kindred were obtained by medical history taking and radiography. ResultsThere were 47 members in the four generations of the Chinese VHL kindred; among them, 18 members were patients with diagnostically proven VHL disease. Their clinical manifestations included: central nervous system(CNS) hemangioblastoma ( n =5), renal cell carcinomas and CNS hemangioblastoma ( n =3), renal cell carcinomas and retinal angiomas ( n =3), renal cell carcinomas and multiple pancreatic cysts ( n =1), renal cell carcinomas and retinal angiomas and multiple pancreatic cysts ( n =2), renal cell carcinomas and CNS hemangioblastomas and multiple pancreatic cysts ( n =1), and multiple pancreatic cysts and multiple renal cysts ( n =1), and multiple pancreatic cysts ( n =2). The common lesions of 18 patients in the large kindred were: renal cell carcinomas (56%), CNS hemangioblastomas(50%), retinal angiomas(28%), and multiple pancreatic cysts(39%). Of the 27 members who volunteered for genetic analysis, all 11 affected family patients who are still alive, including 9 affected family patients and 2 asymptomatic patients, presented a codon 78 from Asn to Ser change at nucleotide 446(A→G) in exon 1. Four members were carriers with the same VHL gene mutation. Two asymptomatic cases were initially diagnosed by genetic testing and subsequently confirmed by radiological imaging and surgery. Members not having the gene mutation had no clinical evidence of VHL disease. ConclusionThe large Chinese kindred with VHL disease was classified as type Ⅰ. The main characteristics of the kindred are higher incidence of renal cell carcinomas and lower incidence of retinal angiomas. The genetic testing played an important role in early detecting asymptomatic patients and the carriers in clinical screening for members in the VHL families. Also, it is important to prevent the transmission of VHL disease to the offspring in the kindred.
出处
《中华医学遗传学杂志》
CAS
CSCD
2004年第1期5-9,共5页
Chinese Journal of Medical Genetics
