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
目的探讨1例合并外耳发育不良的先天性糖基化障碍1y型(congenital disorder of glycosylation type 1y,CDG-1y)患儿的遗传学病因。方法采用家系全外显子测序法(trio-whole exome sequencing,trio-WES)检测相关基因的变异,通过Sanger测...目的探讨1例合并外耳发育不良的先天性糖基化障碍1y型(congenital disorder of glycosylation type 1y,CDG-1y)患儿的遗传学病因。方法采用家系全外显子测序法(trio-whole exome sequencing,trio-WES)检测相关基因的变异,通过Sanger测序法对候选变异进行验证,并对其致病性进行生物信息学预测。结果患者为男性,10岁,主要表现为智力障碍、小头畸形合并先天性外耳发育不良。trio-WES检测发现患儿携带X染色体SSR4基因第4外显子c.302dupC(p.Y102Lfs*2)半合子移码变异,既往未见报道。Sanger测序在患儿父母中均未发现同样的变异,故属于新发变异(de novo)(PS2);在主要人群基因频率数据库中均未收录(PM2)。多种软件预测结果均提示其为致病变异(PP3)。UCSF chimera软件分析提示,该变异可使SSR4蛋白空间结构严重变形,导致生物学功能的丧失(PVS1+PM1)。根据ACMG指南,判断为致病性变异(PVS1+PS2+PM1+PM2+PP3)。结论SSR4基因c.302dupC(p.Y102Lfs*2)可能为患儿罹患CDG-1y的原因。上述发现拓宽了SSR4基因的变异谱以及CDG-1y的表型谱。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.
文摘目的探讨1例合并外耳发育不良的先天性糖基化障碍1y型(congenital disorder of glycosylation type 1y,CDG-1y)患儿的遗传学病因。方法采用家系全外显子测序法(trio-whole exome sequencing,trio-WES)检测相关基因的变异,通过Sanger测序法对候选变异进行验证,并对其致病性进行生物信息学预测。结果患者为男性,10岁,主要表现为智力障碍、小头畸形合并先天性外耳发育不良。trio-WES检测发现患儿携带X染色体SSR4基因第4外显子c.302dupC(p.Y102Lfs*2)半合子移码变异,既往未见报道。Sanger测序在患儿父母中均未发现同样的变异,故属于新发变异(de novo)(PS2);在主要人群基因频率数据库中均未收录(PM2)。多种软件预测结果均提示其为致病变异(PP3)。UCSF chimera软件分析提示,该变异可使SSR4蛋白空间结构严重变形,导致生物学功能的丧失(PVS1+PM1)。根据ACMG指南,判断为致病性变异(PVS1+PS2+PM1+PM2+PP3)。结论SSR4基因c.302dupC(p.Y102Lfs*2)可能为患儿罹患CDG-1y的原因。上述发现拓宽了SSR4基因的变异谱以及CDG-1y的表型谱。
