Epidermolysis bullosa(EB)is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation.Here,we investigated five Chinese families with EB...Epidermolysis bullosa(EB)is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation.Here,we investigated five Chinese families with EB,and eight variants including a novel nonsense variant(c.47G>A,p.W16*)in LAMA3,a known recurrent variant(c.74C>T,p.P25L)in KRT5,2 novel(c.2531T>A,p.V844E;c.6811_6814del,p.R2271fs)and 4 known(c.6187C>T,p.R2063W;c.7097G>A,p.G2366D;c.8569G>T,p.E2857*;c.3625_3635del,p.S1209fs)variants in COL7A1 were detected.Notably,this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay.Our study expands the mutation spectra of Chinese patients with EB.展开更多
目的对一个中国汉族手足复发型单纯型大疱性表皮松解症(Weber-Cockayne type epidermolytic bullosa simplex,EBS-WC)家系进行致病基因检测,探讨KLHL24基因和KRT14基因在EBS发病机制中的相关性,为产前诊断和遗传咨询提供依据。方法提取...目的对一个中国汉族手足复发型单纯型大疱性表皮松解症(Weber-Cockayne type epidermolytic bullosa simplex,EBS-WC)家系进行致病基因检测,探讨KLHL24基因和KRT14基因在EBS发病机制中的相关性,为产前诊断和遗传咨询提供依据。方法提取该家系中4例患者以及5例健康人外周血基因组DNA,扩增KRT5和KRT14基因的全部外显子,以及KLHL24基因的启动子,并测序。以寻常性银屑病外显子测序研究中的676例正常人群为对照。收集先证者皮损组织进行病理检查。结果先证者病理诊断支持单纯型大疱性表皮松解症。所有患者均出现KRT14基因第6外显子第1162位错义突变(c.1162C>T),导致388位胞嘧啶(C)被胸腺嘧啶(T)替换,角蛋白结构中精氨酸被半胱氨酸取代。家系中的正常人和676例无血缘关系的健康人没有发现相同的碱基改变。家系中没有发现KLHL24基因起始密码子突变。结论KRT14基因第6外显子的错义突变是该中国汉族EBS-WC家系患者的致病基因。展开更多
基金This work was financially supported by the National Natural Science Foundation of China(No.81788101)the National Key Research and Development Program of China(No.2016YFC0905100)+1 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2016-I2M-1-002)the Natural Science Foundation of Beijing(No.7172167).
文摘Epidermolysis bullosa(EB)is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation.Here,we investigated five Chinese families with EB,and eight variants including a novel nonsense variant(c.47G>A,p.W16*)in LAMA3,a known recurrent variant(c.74C>T,p.P25L)in KRT5,2 novel(c.2531T>A,p.V844E;c.6811_6814del,p.R2271fs)and 4 known(c.6187C>T,p.R2063W;c.7097G>A,p.G2366D;c.8569G>T,p.E2857*;c.3625_3635del,p.S1209fs)variants in COL7A1 were detected.Notably,this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay.Our study expands the mutation spectra of Chinese patients with EB.
文摘目的对一个中国汉族手足复发型单纯型大疱性表皮松解症(Weber-Cockayne type epidermolytic bullosa simplex,EBS-WC)家系进行致病基因检测,探讨KLHL24基因和KRT14基因在EBS发病机制中的相关性,为产前诊断和遗传咨询提供依据。方法提取该家系中4例患者以及5例健康人外周血基因组DNA,扩增KRT5和KRT14基因的全部外显子,以及KLHL24基因的启动子,并测序。以寻常性银屑病外显子测序研究中的676例正常人群为对照。收集先证者皮损组织进行病理检查。结果先证者病理诊断支持单纯型大疱性表皮松解症。所有患者均出现KRT14基因第6外显子第1162位错义突变(c.1162C>T),导致388位胞嘧啶(C)被胸腺嘧啶(T)替换,角蛋白结构中精氨酸被半胱氨酸取代。家系中的正常人和676例无血缘关系的健康人没有发现相同的碱基改变。家系中没有发现KLHL24基因起始密码子突变。结论KRT14基因第6外显子的错义突变是该中国汉族EBS-WC家系患者的致病基因。
