摘要
Silver-Russell综合征(SRS)是一种导致产前和产后生长迟缓的印迹障碍疾病,通常是由胎儿生长因子IGF2的表观遗传下调引起。SRS的主要遗传原因是11p15染色体甲基化缺失(11p15 LOM)和7号染色体母体单亲二体[upd(7)mat]。近年来,HMGA2、PLAG1、IGF2及CDKN1C被认为是SRS的新责任基因。随着研究的深入进展,新的致病变体被发现,HMGA2基因新突变位点(c.111+1G>T、c.239C>T、c.223C>T、c.193C>T和c.189del)及PLAG1基因新突变位点(c.439del、c.1363del、c.589C>T和c.551delA)通过影响DNA结合导致SRS,IGF2基因新突变位点(c.195delC、c.157+3A>C、c.157+5G>A、c.110_117delinsAGGTAA、c.101G>A、c.78C>G和c.158_159dup等)被认定为与SRS相关。CDKN1C基因突变位点(c.836G>T、c.835C>A和c.947G>A)通过增加蛋白的功能性抑制细胞分裂周期进程导致SRS。
Silver-Russell syndrome(SRS) is a clinically and genetic-ally heterogeneous disorder characterized by growthfailure and dysmorphic features, usually caused by epigenetic downregulation of fetal growth factor IGF2. The major(epi) genetic causes of SRS are loss of methylation on chromosome 11p15(11p15 LOM) and maternal uniparental disomy of chromosome 7(upd(7)mat). Recently, HMGA2, PLAG1, IGF2 and CDKN1C were proposed as the new responsible genes for SRS. With the further development of research, new mutations in HMGA2(c.111+1G>T, c.239C>T, c.223C>T, c.193C>T and c.189del) and PLAG1(c.439del, c.1363del, c.589C>T and c.551delA) lead to SRS by affecting DNA binding, and IGF2 genes(c.195delC, c.157+3A>C, c.157+5G>A, c.110_117delinsAGGTAA, c.101G>A, c.78C>G and c.158_159DUP et al.) were identified as SRS related. CDKN1C mutation sites(c.836G>T, c.835C>A and c.947G>A) lead to SRS by increasing the function of the protein to inhibit cell division cycle progression.
作者
郭子显
霍竞
全宇璐
王涛
张萍萍
罗艳
李娟
李亚丽
GUO Zixian;HUO Jing;QUAN Yulu;WANG Tao;ZHANG Pingping;LUO Yan;LI Juan;LI Yali(Department of Reproductive Genetics,Hebei General Hospital,Shijiazhuang,Hebei 050051,China;North China University of Science and Technology,Tangshan,Hebei 063210,China;Hebei Medical University,Shijiazhuang,Hebei 050071,China;Hebei North University,Zhangjiakou,Hebei 075000,China)
出处
《中国优生与遗传杂志》
2022年第12期2287-2292,共6页
Chinese Journal of Birth Health & Heredity
基金
河北省医学适用技术跟踪项目(GZ2021079)。
