142例胎儿唇腭裂的超声诊断与遗传因素分析

目的探讨胎儿唇腭裂的影像学特征与遗传基础。方法142例病例均接受产前超声系统检查,经过两级医生检查及会诊做出最终诊断。同时收集活产胎儿的胎儿脐带或引产胎儿的大腿肌肉组织,进行全基因组测序(whole genome sequening,WGS),以发现染色体数目异常和拷贝数异常(copy number variations,CNVs)。结果142例孕妇年龄分布为21~41岁,孕周为12~35周。142例胎儿中,男性94例,女性48例,男女比例为1∶0.51。根据唇腭裂的类型,单纯唇裂有84/142例(59.15%),唇裂合并其他系统畸形情况有31/142例(21.83%)。单纯唇腭裂有14/142例(9.86%),唇腭裂合并其他系统畸形情况有13/142例(9.15%)。9.2%(13/142)的胎儿有染色体数目异常,8.4%(12/142)的胎儿检出了致病性CNV。结论对CNVs的检测可以增加胎儿腭裂的遗传检测诊断率,在临床中应重视检测致病性CNVs。

Prenatal diagnosis and genetic analysis in a series of 142 fetuses with Cleft Lip and palate

Objective To study the imaging features of 142 fetuses with cleft lip and explore the genetic basis of these fetuses.Methods A cohort of 142 fetuses with cleft lip(including cleft palate),which were detected by prenatal ultrasound and confirmed by specialist consultants,were collected.The available tissues,including fetal umbilical cord from live-born fetuses or thigh muscle from aborted fetuses,were subject to low pass whole-genome sequencing(WGS),to identify chromosomal anomalies and copy number variations(CNVs).Results The age distribution of 142 pregnant women ranged from 21 to 41 years old and gestational weeks ranged from 12 to 35 weeks.Of these 142 fetuses,there are 94 male fetuses and 48 female fetuses,and the male to female ratio was 1∶0.51.According to the types of cleft lip and palate,there were 84/142 cases(59.15%)of cleft lip alone,and 31/142 cases(21.83%)of cleft lip combined with other systematic malformations.There were 14/142 cases of cleft lip and palate alone(9.86%),and 13/142 cases of cleft lip and palate combined with other system malformations(9.15%).9.2%(13/142)of fetuses had chromosome anomalies,and 8.4%(12/142)of fetuses had a pathogenic CNV.Conclusion The overall genetic diagnosis rate is 17.6%(25/142).The detection rate of chromosome anomalies was 9.2%(13/142).The detection rate of the CNV was 8.4%(12/142).Identification of pathogenic CNVs can increase the genetic diagnosis of cleft lip and palate,and thus attentions should be paid to CNVs analysis.