14例1q21.1远端微缺失/微重复胎儿的产前诊断及遗传咨询

Prenatal diagnosis and genetic counseling of 1q21.1 distal microdeletion/microduplication in 14 fetuses

目的探讨1q21.1远端微缺失/微重复胎儿的临床表型、妊娠结局及随访情况,为产前及再生育咨询提供依据。方法2017年1月至2022年6月在无锡市妇幼保健院产前诊断(染色体核型分析和染色体微阵列分析)的14例1q21.1远端微缺失/微重复胎儿(均为单胎)纳入回顾性分析。总结遗传学和超声检查结果、遗传咨询后的妊娠结局及出生后随访情况。采用描述性统计分析。结果14例胎儿染色体核型分析均未见明显异常。染色体微阵列分析共检出1q21.1远端微缺失8例、微重复6例,片段大小813 kb~4.48 Mb,均包含1q21.1微缺失/微重复综合征的关键区域,为致病性拷贝数变异。8例1q21.1远端微缺失胎儿中,4例产前超声异常,其中左手叠指伴羊水过多1例、小于胎龄儿2例,头围偏小1例;6例行亲代溯源检测显示新发变异4例,2例遗传自表型正常的亲代。6例1q21.1远端微重复胎儿中,4例产前超声提示鼻骨缺失或骨化不全,另2例产前超声未见明显异常;4例行亲代溯源检测示新发变异1例,3例遗传自表型正常的亲代。遗传咨询后,5例胎儿家庭选择终止妊娠,其余9例继续妊娠至分娩。随访9例活产儿至7月龄~5.5岁,生长发育均未见异常。结论染色体微阵列分析在1q21.1远端微缺失/微重复的产前诊断中具有重要价值,致病性拷贝数变异不等同于发病,结合宫内超声及亲代溯源结果进行个性化咨询并长期跟踪随访,对合理指导妊娠结局及再生育具有重要意义。

Objective To explore the clinical phenotypes,pregnancy outcomes,and follow-up of fetuses with 1q21.1 distal microdeletion/microduplication,and to provide a basis for prenatal and genetic counseling.Methods This was a retrospective study involving 14 singleton fetuses with 1q21.1 distal microdeletion/microduplication that were prenatally diagnosed by karyotype analysis and chromosomal microarray analysis(CMA)at Wuxi Maternity and Child Health Care Hospital from January 2017 to June 2022.The results of ultrasound and genetic analysis,pregnancy outcome after genetic counseling,and postnatal follow-up were summarized using descriptive statistical methods.Results All 14 fetuses had normal karyotypes.Out of the 14 cases,CMA indicated 1q21.1 distal microdeletion in eight cases and 1q21.1 distal microduplication in six cases.The fragments ranged from 813 kb to 4.48 Mb,all of which contained the key region of 1q21.1 microdeletion/microduplication syndrome and were pathogenic copy number variations(CNV).Among eight fetuses with distal 1q21.1 microdeletion,four cases had abnormal prenatal ultrasound findings,including one case with overlapping fingers of left hand and polyhydramnios,two were small for gestational age,and one with small head circumference.Among the six cases who underwent parental origin detection,the microdeletions were de novo in four fetuses and two fetuses were inherited from the parent with normal phenotype.As for six fetuses with distal 1q21.1 microduplication,nasal bone absence or hypoplasia was shown by ultrasound in four cases and no obvious abnormality was found in the other two cases.Parental origin detection was performed in four cases,which found that one case was de novo and the other three cases were inherited from their phenotypically normal parents.After genetic counseling,five families chose to terminate the pregnancies and the remaining nine cases continued the pregnancies to delivery.The last follow-up showed that all of the nine live births grew well,whose ages ranged from seven months to half past five years old.Conclusions CMA is of great value in prenatal diagnosis of 1q21.1 distal microdeletion/microduplication.Ones carrying pathogenic CNV may not develop the disease.Combined with ultrasound findings and parental genetic tracing results,individualized genetic counseling and long-term follow-up are of great importance for reasonable guidance in pregnancy outcome and reproduction.