We analyzed the clinical features and NF1 gene mutation in a Chinese pedigree of neurofibromatosis type 1（NF1）. Three members of this family were NF1 patients presenting with different clinical phenotypes and the ot...We analyzed the clinical features and NF1 gene mutation in a Chinese pedigree of neurofibromatosis type 1（NF1）. Three members of this family were NF1 patients presenting with different clinical phenotypes and the others were asymptomatic. Exons of NF1 were amplified by polymerase chain reaction, sequenced, compared with a reference database. One novel NF1 frame-shift mutation c.703_704delTA, which resulted in a premature stop signal at codon 720 and the synthesis of truncated, was revealed. This mutation segregated with the NF1 members is likely responsible for the pathogenesis of NF1 in the family.展开更多
Neurofibromatosis type 1 is a common autosomal dominant disorder with a high rate of penetrance. It is caused by the mutation of the tumor suppressor gene NF1, which encodes neurofibromin. The main function of neurofi...Neurofibromatosis type 1 is a common autosomal dominant disorder with a high rate of penetrance. It is caused by the mutation of the tumor suppressor gene NF1, which encodes neurofibromin. The main function of neurofibromin is down-regulating the biological activity of the proto-oncoprotein Ras by acting as a Ras-specific GTPase activating protein. In this study, we identified a Chinese family affected with neurofibromatosis type 1. The known gene NF1 associated with NF1 was studied by linkage analysis and by direct sequencing of the entire coding region and exon-intron boundaries of the NF1 gene. The R1947X mutation of NF1 was identified, which was co-segregated with affected individuals in the Chinese family, but not present in unaffected family members. This is the first report, which states that the R1947X mutation of NF1 may be one of reasons for neurofibromatosis type 1 in Chinese population.展开更多
目的:对三例散发I型神经纤维瘤病(neurofibromatosis type 1,NF1)患者进行NFl基因检测。方法:提取3例患者及5名正常家系成员和100例无NF1家族史的正常人外周血DNA。PCR扩增NF1基因全部外显子及侧翼序列,经纯化后采用Sanger测序法对目标...目的:对三例散发I型神经纤维瘤病(neurofibromatosis type 1,NF1)患者进行NFl基因检测。方法:提取3例患者及5名正常家系成员和100例无NF1家族史的正常人外周血DNA。PCR扩增NF1基因全部外显子及侧翼序列,经纯化后采用Sanger测序法对目标基因区域进行测序。结果:患者1,患者2和患者3分别检测到39号外显子发生碱基G缺失(c.5635 delG),47号外显子大片段碱基缺失(c.7041～7062+4del),21号外显子发生碱基A、C缺失(c.2714-2715delAC)。患者家属及100例正常对照均未检测到上述突变。结论:本研究在3例NFl患者中发现NFl基因3种新突变。展开更多
目的:明确Ⅰ型神经纤维瘤病(neurofibromatosis type 1,NF1)一家系的致病基因。方法:本研究招募了一例NF1患儿,具有典型的皮肤咖啡牛奶斑、腋窝雀斑及神经纤维瘤。切除眼眶、上颚肿物行组织病理学和免疫组化检查,提取患儿及其家庭成员...目的:明确Ⅰ型神经纤维瘤病(neurofibromatosis type 1,NF1)一家系的致病基因。方法:本研究招募了一例NF1患儿,具有典型的皮肤咖啡牛奶斑、腋窝雀斑及神经纤维瘤。切除眼眶、上颚肿物行组织病理学和免疫组化检查,提取患儿及其家庭成员的外周血DNA,进行了全外显子组测序(Exome sequencing, WES)和Sanger测序。结果:结果显示眼眶、上颚肿物组织病理及免疫组化结果提示神经纤维瘤,在该NF1患儿中发现了一种新发致病性杂合突变NF1 c.204+2T>G,该突变导致氨基酸发生剪接突变。其父母无致病基因,该患儿为自发突变。结论:本研究鉴定一例NF1患儿的致病基因NF1 c.204+2T>G突变,丰富了NF1基因数据库。展开更多
基金Supported by the National Major Scientific Equipment Program(No.2012YQ12008005)
文摘We analyzed the clinical features and NF1 gene mutation in a Chinese pedigree of neurofibromatosis type 1（NF1）. Three members of this family were NF1 patients presenting with different clinical phenotypes and the others were asymptomatic. Exons of NF1 were amplified by polymerase chain reaction, sequenced, compared with a reference database. One novel NF1 frame-shift mutation c.703_704delTA, which resulted in a premature stop signal at codon 720 and the synthesis of truncated, was revealed. This mutation segregated with the NF1 members is likely responsible for the pathogenesis of NF1 in the family.
基金This work was supported by the National Natural Science Foundation of China(No.30571677)the National Basic Research Program of China(973 Program)(No.2007CB512000).
文摘Neurofibromatosis type 1 is a common autosomal dominant disorder with a high rate of penetrance. It is caused by the mutation of the tumor suppressor gene NF1, which encodes neurofibromin. The main function of neurofibromin is down-regulating the biological activity of the proto-oncoprotein Ras by acting as a Ras-specific GTPase activating protein. In this study, we identified a Chinese family affected with neurofibromatosis type 1. The known gene NF1 associated with NF1 was studied by linkage analysis and by direct sequencing of the entire coding region and exon-intron boundaries of the NF1 gene. The R1947X mutation of NF1 was identified, which was co-segregated with affected individuals in the Chinese family, but not present in unaffected family members. This is the first report, which states that the R1947X mutation of NF1 may be one of reasons for neurofibromatosis type 1 in Chinese population.
文摘目的:对三例散发I型神经纤维瘤病(neurofibromatosis type 1,NF1)患者进行NFl基因检测。方法:提取3例患者及5名正常家系成员和100例无NF1家族史的正常人外周血DNA。PCR扩增NF1基因全部外显子及侧翼序列,经纯化后采用Sanger测序法对目标基因区域进行测序。结果:患者1,患者2和患者3分别检测到39号外显子发生碱基G缺失(c.5635 delG),47号外显子大片段碱基缺失(c.7041～7062+4del),21号外显子发生碱基A、C缺失(c.2714-2715delAC)。患者家属及100例正常对照均未检测到上述突变。结论:本研究在3例NFl患者中发现NFl基因3种新突变。
