Family history of von Hippel-Lindau disease was uncommon in Chinese patients: suggesting the higher frequency of de novo mutations in VHL gene in these patients
Family history of von Hippel-Lindau disease was uncommon in Chinese patients: suggesting the higher frequency of de novo mutations in VHL gene in these patients
复制标题
von Hippel-Lindau病家族史在中国患者中并不常见：表明这些患者中VHL基因新生突变的频率较高
DOI：
10.1038/jhg.2012.10
复制
发表时间：
2012-04-01
影响因子：
3.5
通讯作者：
Gong, Kan
中科院分区：
文献类型：
--
作者：
Wu, Pengjie;Zhang, Ning;Gong, Kan
Von Hippel-Lindau （VHL）病是由VHL肿瘤抑制基因种系突变引起的常染色体显性家族性癌症综合征。主要表现为中枢神经系统和视网膜血管母细胞瘤、肾细胞癌或囊肿、嗜铬细胞瘤、胰腺囊肿和肿瘤、内淋巴囊瘤、附睾和阔韧带乳头状囊腺瘤。本研究采用PCR-直接测序和通用引物定量荧光多重PCR （UPQFM-PCR）对16例临床诊断为VHL疾病的患者进行VHL突变检测。PCR-direct测序检测到12个种系突变（75%,12/16），其中c.451A>T/p为新突变。1例先证者中发现Ile151Phe，此前未见报道。UPQFM-PCR发现2个大缺失（12.5%,2/16）。其余2例患者携带非典型致病突变，包括1例沉默突变（c.481C>A/p.Arg161Arg）和1例3'-UTR突变（c.642+70C>A）。值得注意的是，56.3%（9/16）的先证者没有VHL疾病家族史，这表明中国患者的新生突变频率更高。我们还总结了文献中发表的中国VHL患者的VHL突变发现，以提供有关中国VHL患者VHL突变谱的信息。人类遗传学杂志（2012）57,238-243；doi: 10.1038 / jhg.2012.10;2012年2月23日在线发布
Von Hippel-Lindau (VHL) disease is an autosomal dominant familial cancer syndrome caused by germline mutations in VHL tumor suppressor gene. It is characterized by hemangioblastoma in central nervous system and retina, renal cell carcinoma or cyst, pheochromocytoma, pancreatic cyst and tumor, endolymphatic-sac tumor, and papillary cystadenoma in epididymis and broad ligament. Here, we used PCR-direct sequencing and universal primer quantitative fluorescent multiplex PCR (UPQFM-PCR) to detect VHL mutations in 16 patients clinically diagnosed with VHL disease. PCR-direct sequencing detected 12 germline mutations (75%, 12/16), in which a novel mutation of c.451A>T/p.Ile151Phe found in one proband had not been reported previously. UPQFM-PCR found two large deletions (12.5%, 2/16). The two remaining patients carried non-typical disease-causing mutations, including one silent mutation (c.481C>A/p.Arg161Arg) and one mutation in 3'-UTR (c.642+70C>A). Remarkably, 56.3% (9/16) probands did not have family history of VHL disease, suggesting the higher frequency of de novo mutations in Chinese patients. We also summarized Chinese VHL disease patients with VHL mutation findings published in the literature to provide information about the spectrum of VHL mutations in Chinese VHL disease patients. Journal of Human Genetics (2012) 57, 238-243; doi:10.1038/jhg.2012.10; published online 23 February 2012