肠道病毒71型(Enterovirus 71,EV71)为小RNA病毒科肠道病毒属A组病毒的代表株,感染可引发手足口病(Hand-foot and mouth disease,HFMD),严重危害儿童健康。EV713C蛋白酶(3C)是其编码的主要蛋白酶之一,在病毒多蛋白加工过程中发挥关键作...肠道病毒71型(Enterovirus 71,EV71)为小RNA病毒科肠道病毒属A组病毒的代表株,感染可引发手足口病(Hand-foot and mouth disease,HFMD),严重危害儿童健康。EV713C蛋白酶(3C)是其编码的主要蛋白酶之一,在病毒多蛋白加工过程中发挥关键作用,同时切割细胞蛋白以利于病毒复制。为进一步了解EV71与宿主间博弈关系,本课题组前期以3C为诱饵进行酵母双杂交实验,筛选与3C发生相互作用的可能底物,钓取到锌指MYM型蛋白2(Zinc finger MYM-type protein 2,ZMYM2)。ZMYM2是一种具有锌指结构的转录因子,与细胞中重要的抗病毒小体PML核体(PML nuclear bodies,PML-NBs)的形成及稳定性相关。本文选择3C与ZMYM2关系展开研究,确证二者相互作用并初探生物学功能。首先通过免疫共沉淀实验确证3C与ZMYM2之间存在相互作用;随后分析功能,发现过表达ZMYM2抑制EV71复制;敲减内源ZMYM2有利于EV71的复制;分析3C对ZMYM2影响,发现3C剂量依赖性切割ZMYM2,ZMYM2上至少具有2个3C的识别位点。本研究为解析ZMYM2功能及进一步了解EV71与宿主先天免疫间博弈关系提供了新的实验证据。展开更多
BACKGROUND Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities(NECRC)is a rare,autosomal,dominant neurological disorder caused by mutations in the ZMYM2 gene.To date,the clinical and...BACKGROUND Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities(NECRC)is a rare,autosomal,dominant neurological disorder caused by mutations in the ZMYM2 gene.To date,the clinical and functional characteristics of the novel ZMYM2 mutation c.2090_2091del have not yet been reported.CASE SUMMARY The patient was an 18.5-mo-old Chinese boy with motor and language delay,microcephaly,facial dysmorphism,moderate malnutrition,single palmar crease on the left hand,synpolydactyly of the right foot,hypotonia and feeding problems.The boy who was diagnosed with NECRC was enrolled in the First Affiliated Hospital,Henan University of Chinese Medicine,and his clinical data were collected.From the whole-exon sequencing(WES)data,the pathogenic SNVs/InDels were identified,and the molecular findings were characterized.WES revealed that the heterozygous variant in the ZMYM2 gene was c.2090_20-91del,p.Ser697TrpfsTer3,a frameshift mutation,which is a NECRC-related gene mutation.CONCLUSION We performed a systematic literature review to identify and characterize NECRC.Substantial evidence from the literature indicated that patients with ZMYM2 gene mutation showed different degrees of intellectual disability,motor and language retardation,facial dysmorphism,and a few had congenital heart defects,kidney and urinary tract abnormalities.Early diagnosis and prompt management with comprehensive rehabilitation training are beneficial,but may not improve long-term outcomes.展开更多
基金Supported by the National Natural Science Foundation of China,No.82205190the Foundation for Distinguished Young Talents in Higher Education of Henan,No.[2018]16
文摘BACKGROUND Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities(NECRC)is a rare,autosomal,dominant neurological disorder caused by mutations in the ZMYM2 gene.To date,the clinical and functional characteristics of the novel ZMYM2 mutation c.2090_2091del have not yet been reported.CASE SUMMARY The patient was an 18.5-mo-old Chinese boy with motor and language delay,microcephaly,facial dysmorphism,moderate malnutrition,single palmar crease on the left hand,synpolydactyly of the right foot,hypotonia and feeding problems.The boy who was diagnosed with NECRC was enrolled in the First Affiliated Hospital,Henan University of Chinese Medicine,and his clinical data were collected.From the whole-exon sequencing(WES)data,the pathogenic SNVs/InDels were identified,and the molecular findings were characterized.WES revealed that the heterozygous variant in the ZMYM2 gene was c.2090_20-91del,p.Ser697TrpfsTer3,a frameshift mutation,which is a NECRC-related gene mutation.CONCLUSION We performed a systematic literature review to identify and characterize NECRC.Substantial evidence from the literature indicated that patients with ZMYM2 gene mutation showed different degrees of intellectual disability,motor and language retardation,facial dysmorphism,and a few had congenital heart defects,kidney and urinary tract abnormalities.Early diagnosis and prompt management with comprehensive rehabilitation training are beneficial,but may not improve long-term outcomes.
