基于河北全省联动的孕妇耳聋基因筛查新模式的理论与实践

The Theory and Practice of a New Mode of Province-Wide Genetic Screening for Deafness in Pregnant Women in Hebei

目的创立基于河北全省多中心联动的孕妇耳聋基因筛查新模式,探讨聋病出生缺陷防控效果。方法由河北省卫生健康委员会主导组织成立河北省孕妇耳聋基因筛查项目技术专家组,在全省范围内实施统一培训、统一宣教,建立覆盖全省的孕妇耳聋基因筛查新模式。采用高通量测序技术对辖区内孕妇免费进行常见耳聋4个基因20个位点筛查,由经过培训的医生负责结果解读与遗传咨询。对阳性孕妇的配偶进行相应基因全序列测序,发现耳聋高危家庭并施行产前诊断与生育指导。阳性孕妇生育后给予定期随访,发现耳聋患儿及时转诊、及时干预。结果2019年9月1日至2021年8月31日间,河北省各地市建档孕妇1,053,232例,其中709,386例孕妇选择进行常见耳聋基因筛查,2年筛查覆盖率达67.4%(709,386/1,053,232),共检出常见耳聋基因携带者41,216例,未通过率达5.81%(41,216/709,386),25,546例阳性孕妇进行了面对面遗传咨询,遗传咨询率为62%(25,546/41,216)。34,188例GJB2或SLC26A4突变携带者的配偶中有9,778例选择进行相应基因全序列检测,配偶检测率为28.6%(9,778/34,188),783对(8%,783/9,778)夫妇被证实同为GJB2或SLC26A4基因致病变异携带者,预测后代出现耳聋的风险为25%;164对双阳夫妇经知情同意后选择进行产前诊断,产前诊断率为20.94%(164/783)。发现36例胎儿为GJB2或SLC26A4基因复合杂合变异,其中33例家庭选择终止妊娠,3例自然分娩。4,892例孕妇检测发现为线粒体MT-RNR1基因突变携带者,给予咨询指导孕妇及其母系家族成员避免使用耳毒性药物。结论河北省孕妇遗传性耳聋基因携带率为5.819%,为41,216名孕妇明确了常见耳聋基因携带情况及进行遗传咨询与生育指导,将耳聋预防窗口前移至出生前,形成了全省联动的聋病预防新模式。

Objectives To report a new province-wide model of genetic screening for deafness pregnant women in Hebei,and to evaluate its effects in the prevention and control of deafness.Method An expert group was established by the Health Commission of Hebei Province for a genetic screening for deafness project in pregnant women,which involved province-wide free deafness gene screening,followed by interpretation and consultation by providers with standardized training,which covered genetic counseling,referral and diagnosis related to combined hearing and genetic screening in newborns.NGS sequencing was used to screen 20 variation sites on 4 common deafness genes in pregnant women.The results were interpreted by senior level physicians.Spouses of carrier were advised to complete genetic screening tests.Genetic counseling and post-partum follow ups were provided to high-risk couples.Timely referrals and interventions were provided to children with deafness.Results From September 1,2019 to August 31,2021,among all pregnant women in Hebei(1,053,232),67.40%(709,386)received deafness gene screening,of whom 5.81%(41,216/709,386)were found to be carriers.Of these carriers,62%(25,546/41,216)opted for genetic counseling.In 28.6%(9,778)of the 34,188 GJB2 or SLC26A4 mutation carriers,their spouses accepted genetic sequencing,of whom 783(8%)were found to carry the same deafness gene mutations(either GJB2 or SLC26A4).These couples were informed of the relatively high(25%)risk of deafness for their offspring,and 20.94%(164/783)of them opted for prenatal diagnostic testing.GJB2 or SLC26A4 gene complex heterozygous variations were identified in 36 fetuses,and pregnancy was terminated in 33 of them while the rest 3 were carried to labor.4,892 women were identified as mtDNA carriers and advised to strictly avoid exposure to aminoglycoside antibiotics to prevent ototoxic hearing damage.Conclusion The rate of genetic deafness gene variants carriers among pregnant women in Hebei Province is 5.819%.These carriers are advised to have genetic counseling.A new model of province-wide deafness prevention through combined hearing and genetic screening during pregnancy is established.