Kelch-like family member 17(KLHL17)is predominantly expressed in the brain and plays a crucial role in neuronal development and function,deletions and/or mutations in KLHL17 have been linked to neurodevelopmental diso...Kelch-like family member 17(KLHL17)is predominantly expressed in the brain and plays a crucial role in neuronal development and function,deletions and/or mutations in KLHL17 have been linked to neurodevelopmental disorders in humans,e.g.,intellectual disability,autism spectrum disorder,and infantile spasms,but the etiology and pathogenesis remain largely enigmatic.1,2 As a member of the family of the Kelch proteins,KLHL17 contains an N-terminal BTB/POZ domain followed by a BACK domain and four to six tandem Kelch motifs at the C-terminal region(Fig.S1A).1,3 Previously,we identified a novel de novo variant in KLHL17(c.701C>T;p.P234L)in a cohort of 225 Chinese children with developmental delay/intellectual disability based on whole-exome sequencing(1/225),the mutation located in the BACK domain,a very high conversed region(Fig.S1B),and the affected boy presented with developmental delay,intellectual disability,hypotonia,and abnormal brainstem auditory evoked potential signal.4 The finding may offer a new clue to investigate the molecular pathogenesis of KLHL17 gene in neurodevelopmental disorders.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funded by the National Natural Science Foundation of China(No.82160620)the Natural Science Foundation of Guangxi Province,China(No.2023GXNSFAA026036)the Guangxi College Students Innovation and Entrepreneurship Training Program(China)(No.S202310601164).
文摘Kelch-like family member 17(KLHL17)is predominantly expressed in the brain and plays a crucial role in neuronal development and function,deletions and/or mutations in KLHL17 have been linked to neurodevelopmental disorders in humans,e.g.,intellectual disability,autism spectrum disorder,and infantile spasms,but the etiology and pathogenesis remain largely enigmatic.1,2 As a member of the family of the Kelch proteins,KLHL17 contains an N-terminal BTB/POZ domain followed by a BACK domain and four to six tandem Kelch motifs at the C-terminal region(Fig.S1A).1,3 Previously,we identified a novel de novo variant in KLHL17(c.701C>T;p.P234L)in a cohort of 225 Chinese children with developmental delay/intellectual disability based on whole-exome sequencing(1/225),the mutation located in the BACK domain,a very high conversed region(Fig.S1B),and the affected boy presented with developmental delay,intellectual disability,hypotonia,and abnormal brainstem auditory evoked potential signal.4 The finding may offer a new clue to investigate the molecular pathogenesis of KLHL17 gene in neurodevelopmental disorders.
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。
