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
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
BACKGROUND Pancreatic mixed serous-neuroendocrine neoplasms(MSNNs)are mixed tumors containing two components with different pathologies,namely,pancreatic serous cystic neoplasm(PSCN)and pancreatic neuroendocrine tumor...BACKGROUND Pancreatic mixed serous-neuroendocrine neoplasms(MSNNs)are mixed tumors containing two components with different pathologies,namely,pancreatic serous cystic neoplasm(PSCN)and pancreatic neuroendocrine tumor(PanNET).For MSNNs,diffuse PSCN involving the whole pancreas is extremely rare,with only eight previous case reports.CASE SUMMARY A 45-year-old Chinese woman,with a free previous medical history and no obvious symptoms,was found to have a pancreatic neoplasm and admitted to our hospital for further diagnosis in March 2018.Abdominal palpation revealed a painless,mobile mass in the epigastrium,and no abnormalities were observed in an examination of the nervous system and ocular system.A computed tomography scan showed multiple cystic lesions involving the whole pancreas ranging in diameter from 0.4 to 2 cm and also revealed an enhanced mass,2.2 cm in diameter,in the head of the pancreas.Moreover,multiple cysts were found in the kidneys bilaterally,and the right lobe of the liver contained a small cyst.A Whipple operation with total pancreatectomy and splenectomy was performed.A diagnosis of pancreatic MSNN was established,consisting of diffuse serous microcystic cystadenoma with a concomitant grade 2 PanNET.Of note,the patient had no personal or family history of Von Hippel-Lindau syndrome or other disease.CONCLUSION We report the first case of MSNN with a diffuse PSCN component involving the entire pancreas in a Chinese woman.It is important to be aware of its relationship with VHL syndrome,and close clinical follow-up is recommended.展开更多
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.
基金National Natural Science Foundation of China,No.81702596
文摘BACKGROUND Pancreatic mixed serous-neuroendocrine neoplasms(MSNNs)are mixed tumors containing two components with different pathologies,namely,pancreatic serous cystic neoplasm(PSCN)and pancreatic neuroendocrine tumor(PanNET).For MSNNs,diffuse PSCN involving the whole pancreas is extremely rare,with only eight previous case reports.CASE SUMMARY A 45-year-old Chinese woman,with a free previous medical history and no obvious symptoms,was found to have a pancreatic neoplasm and admitted to our hospital for further diagnosis in March 2018.Abdominal palpation revealed a painless,mobile mass in the epigastrium,and no abnormalities were observed in an examination of the nervous system and ocular system.A computed tomography scan showed multiple cystic lesions involving the whole pancreas ranging in diameter from 0.4 to 2 cm and also revealed an enhanced mass,2.2 cm in diameter,in the head of the pancreas.Moreover,multiple cysts were found in the kidneys bilaterally,and the right lobe of the liver contained a small cyst.A Whipple operation with total pancreatectomy and splenectomy was performed.A diagnosis of pancreatic MSNN was established,consisting of diffuse serous microcystic cystadenoma with a concomitant grade 2 PanNET.Of note,the patient had no personal or family history of Von Hippel-Lindau syndrome or other disease.CONCLUSION We report the first case of MSNN with a diffuse PSCN component involving the entire pancreas in a Chinese woman.It is important to be aware of its relationship with VHL syndrome,and close clinical follow-up is recommended.
