CTCF基因突变致胎儿不良妊娠结局的遗传学分析

Genetic analysis of a case of CTCF gene mutation in fetus associated with adverse outcome

目的探讨CTCF基因致病突变的产前遗传学分析及咨询。方法运用染色体核型分析、荧光原位杂交技术(FISH)、染色体微阵列分析(CMA)及全外显子组测序技术(WES)对一例产前超声发现双侧肾脏回声增强结构模糊的胎儿进行产前遗传学检测。结果核型分析、荧光原位杂交技术、染色体微阵列分析未见异常,家系全外显子测序检测到胎儿CTCF基因存在新发变异c.944_951dup,为移码突变,导致318位甘氨酸密码子(GGT)被替换为组氨酸密码子(CAC),并在第18个密码子后终止(p.Gly318Hisfs*18),产生截短蛋白质。CTCF基因突变可致罕见常染色体显性智力障碍21型,胎儿期尚未见报道。结论本例为首次在胎儿期检出CTCF基因致病突变,推测双肾回声增强结构模糊为该基因突变相关的一种新的胎儿期表型。全外显子组测序技术在产前检测出罕见致病突变的病例需重视检测前后的咨询。

Objective To explore the genetic analysis and counseling of pathogenic CTCF mutation in fetus.Methods Chromosome karyotype analysis,Fluorescence in situ hybridization(FISH),chromosome microarray analysis(CMA)and whole exome sequencing(WES)were used to detect the fetus with poorly structured bilateral hyperechogenic kidneys.Resuts Karyotype analysis,FISH and CMA were normal.A de novo frameshift mutation c 944_951dup(p.G318Hfs*18)of CTCF was detected by WES resulting truncated protein.It can cause"Mental retar dation,autosomal dominant 21",which has not been reported in fetuses.Conclusion In this case,the pathogenic mutation in CTCF was first detected in fetus.The poorly structured bilateral hyperechogenic kidneys may be a novel fetal clinical feature associated with the mutation in CTCF.Pretest and protest counseling should be well done,especially when the rare pathogenic mutations are detected by WES.