The pancreatic manifestations seen in patients with von Hippel-Lindau(VHL) disease are subdivided into 2 categories:pancreatic neuroendocrine tumors(NET),and cystic lesions,including simple cyst and serous cystadenoma...The pancreatic manifestations seen in patients with von Hippel-Lindau(VHL) disease are subdivided into 2 categories:pancreatic neuroendocrine tumors(NET),and cystic lesions,including simple cyst and serous cystadenoma.The VHL-associated cystic lesions are generally asymptomatic and do not require any treatment,unless they are indistinguishable from other cystic tumor types with malignant potential.Because pancreatic NET in VHL disease are non-functioning and have malignant potential,it is of clinical importance to find and diagnose these as early as possible.It will be recommended that comprehensive surveillance using dynamic computed tomography for abdominal manifestations,including pancreatic NET,should start from the age of 15 years in VHL patients.Unlike sporadic non-functioning NET without VHL disease,in which surgical resection is generally recommended,VHL patients at lower metastatic risk of pancreatic NET should be spared the risks of operative resection.展开更多
Von Hippel-Lindau(VHL)综合征是一种较为罕见的常染色体显性遗传疾病,可引起包括中枢神经系统在内的多系统肿瘤。VHL基因是一种抑癌基因,VHL综合征由VHL基因突变引起,VHL基因通过促进缺氧诱导因子1α(HIF-1α)降解导致疾病发生,它通过...Von Hippel-Lindau(VHL)综合征是一种较为罕见的常染色体显性遗传疾病,可引起包括中枢神经系统在内的多系统肿瘤。VHL基因是一种抑癌基因,VHL综合征由VHL基因突变引起,VHL基因通过促进缺氧诱导因子1α(HIF-1α)降解导致疾病发生,它通过编码VHL蛋白来调控其mRNA,在缺氧条件下,导致血管内皮生长因子过表达,影响肿瘤的生长浸润。随着基因检测技术日益成熟,VHL综合征的筛查与治疗逐渐出现了多种手段。因为VHL综合征具有遗传性,深入研究患者致病基因类型特点并结合临床表现,有助于深一步挖掘VHL综合征的发病机制,更好地完善基因靶向药物的研究,从而为患者及其家属提供更好的医疗指导。展开更多
Von Hippel-Lindau（VHL）综合征是一种常染色体显性遗传的家族性多系统肿瘤综合征，为VHL基因突变或缺失所致。本文通过对1例VHL综合征患者的临床特点进行分析，并就该病发病机制、临床表现、基因诊断以及治疗的国内外研究进展进行讨...Von Hippel-Lindau（VHL）综合征是一种常染色体显性遗传的家族性多系统肿瘤综合征，为VHL基因突变或缺失所致。本文通过对1例VHL综合征患者的临床特点进行分析，并就该病发病机制、临床表现、基因诊断以及治疗的国内外研究进展进行讨论，以加深临床医师对本病的认识。展开更多
Von Hippel-Lindau（VHL）综合征是一种罕见的常染色体显性遗传性疾病，胰腺是易被累及的腹部器官之一，包括胰腺单纯性囊肿、浆液性囊腺瘤及神经内分泌肿瘤等。VHL综合征相关胰腺神经内分泌肿瘤（VHL-pNEN）多无功能，但有恶变倾向，...Von Hippel-Lindau（VHL）综合征是一种罕见的常染色体显性遗传性疾病，胰腺是易被累及的腹部器官之一，包括胰腺单纯性囊肿、浆液性囊腺瘤及神经内分泌肿瘤等。VHL综合征相关胰腺神经内分泌肿瘤（VHL-pNEN）多无功能，但有恶变倾向，治疗措施包括定期随访、手术治疗及药物治疗等。VHL-pNEN的恶性程度较散发型pNEN低，预后亦较好，应慎重选择手术治疗。手术指征包括肿瘤最大径≥3 cm、肿瘤倍增时间〈500 d、VHL基因发生3号外显子突变、影像学检查疑有恶性表现、功能性pNEN病灶等。手术方式应尽可能保留有功能的胰腺实质。即使无法根治切除的恶性pNEN患者，积极的内科治疗仍可能使患者获得长期生存。展开更多
Background Von Hippel-Lindau （VHL） syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs.The genetic basis of VHL in Southern Chinese ...Background Von Hippel-Lindau （VHL） syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs.The genetic basis of VHL in Southern Chinese is largely unknown.In this study,we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.Methods Nine probands with clinical features of VHL,two symptomatic and eight asymptomatic family members were included in this study.Prenatal diagnosis was performed twice for one proband.Two probands had only isolated bilateral phaeochromocytoma.The VHL gene was screened for mutations by polymerase chain reaction,direct sequencing and multiplex ligation-dependent probe amplification （MLPA）.Results The nine probands and the two symptomatic family members carried heterozygous germline mutations.Eight different VHL mutations were identified in the nine probands.One splicing mutation,NM_000551.2：c.463＋1G〉T,was novel.The other seven VHL mutations,c.233A〉G [p.Asn78Ser],c.239G〉T [p.Ser80lle],c.319C〉G [p.Arg107Gly],c.481C〉T [p.Arg161X],c.482G〉A [p.Arg161GIn],c.499C〉T [p.Arg167Trp] and an exon 2 deletion,had been previously reported.Three asymptomatic family members were positive for the mutation and the other five tested negative.In prenatal diagnosis,the fetuses were positive for the mutation.Conclusions Genetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma.Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis.DNA-based diagnosis can have an important impact on clinical management for VHL families.展开更多
基金Supported by The Health and Labor Sciences Research Grant for a nationwide clinical survey and establishment of guidelines in the diagnosis and treatment for von Hippel-Lindau disease in Japan
文摘The pancreatic manifestations seen in patients with von Hippel-Lindau(VHL) disease are subdivided into 2 categories:pancreatic neuroendocrine tumors(NET),and cystic lesions,including simple cyst and serous cystadenoma.The VHL-associated cystic lesions are generally asymptomatic and do not require any treatment,unless they are indistinguishable from other cystic tumor types with malignant potential.Because pancreatic NET in VHL disease are non-functioning and have malignant potential,it is of clinical importance to find and diagnose these as early as possible.It will be recommended that comprehensive surveillance using dynamic computed tomography for abdominal manifestations,including pancreatic NET,should start from the age of 15 years in VHL patients.Unlike sporadic non-functioning NET without VHL disease,in which surgical resection is generally recommended,VHL patients at lower metastatic risk of pancreatic NET should be spared the risks of operative resection.
文摘Background Von Hippel-Lindau （VHL） syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs.The genetic basis of VHL in Southern Chinese is largely unknown.In this study,we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.Methods Nine probands with clinical features of VHL,two symptomatic and eight asymptomatic family members were included in this study.Prenatal diagnosis was performed twice for one proband.Two probands had only isolated bilateral phaeochromocytoma.The VHL gene was screened for mutations by polymerase chain reaction,direct sequencing and multiplex ligation-dependent probe amplification （MLPA）.Results The nine probands and the two symptomatic family members carried heterozygous germline mutations.Eight different VHL mutations were identified in the nine probands.One splicing mutation,NM_000551.2：c.463＋1G〉T,was novel.The other seven VHL mutations,c.233A〉G [p.Asn78Ser],c.239G〉T [p.Ser80lle],c.319C〉G [p.Arg107Gly],c.481C〉T [p.Arg161X],c.482G〉A [p.Arg161GIn],c.499C〉T [p.Arg167Trp] and an exon 2 deletion,had been previously reported.Three asymptomatic family members were positive for the mutation and the other five tested negative.In prenatal diagnosis,the fetuses were positive for the mutation.Conclusions Genetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma.Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis.DNA-based diagnosis can have an important impact on clinical management for VHL families.
