基于孕前优生平台的育龄女性假肥大型肌营养不良症携带者筛查模式

Carrier screening model for Duchenne muscular dystrophy for women of reproductive age based on a pre-pregnancy birth defect control platform

目的探索在孕前优生健康检查平台中建立育龄期女性假肥大型肌营养不良(Duchenne muscular dystrophy,DMD)致病基因携带者筛查模式,提高携带者的检出率。方法应用速率法/紫外分光光度法进行血清酶学检测,对2017年10月至2019年10月在杭州市参加国家免费孕前优生健康检查的61870名育龄女性进行肌酸磷酸肌酶(creatine kinase,CK)测定,针对CK高于阈值(≥200 U/L)者及有DMD家族史女性进行DMD基因检测。对确诊的携带者进行遗传咨询和随访。结果通过对61870名育龄女性CK检测,确定CK酶增高人数1078人,复查率57.33%(618/1078);对复查检测结果异常的120人进行基因检测,其中6人确定为DMD致病基因携带者;DMD家族史者基因检测33人,确定DMD致病基因携带者13人;筛查出1例DMD胎儿,经遗传咨询后孕妇选择终止妊娠。结论以国家免费孕前优生健康检查人群为主体,利用CK检测筛查DMD基因携带者是降低DMD患儿出生率的有效途径之一。

Objective To establish a screening model for females of reproductive age carrying Duchenne muscular dystrophy(DMD)variants based on a current community health examination platform.Methods A total of 61870 participants were recruited between October 2017 and October 2019.Serum creatine kinase(CK)was measured with a Roche Cobasc 701/702 using an enzymatic rate method.Genetic testing was offered to those with a CK level of≥200 U/L.For carriers of DMD variants,genetic counseling and follow up were provided.Results For the 61870 females participating in the program,1078 were found with raised serum CK(≥200 U/L),of which 618(57.33%)accepted CK re-measurement after at least a two-week interval.One hundred and twenty cases were found with sustained serum CK elevation,of which 6 were confirmed to be definite DMD carriers regardless of family history.Genetic testing was provided to 33 females with a family history for DMD,and 13 were determined as definite carriers.An affected fetus was detected by prenatal diagnosis.After genetic counseling,the parents had opted induced abortion.Conclusion Large-scale DMD carrier screening through a three-step approach based on the current community health examination platform is both feasible and cost effective.