NIPT-plus提示3pter-p25缺失综合征和Pallister-Killian综合征高风险胎儿1例的遗传学分析

Genetic analysis of one case with high risk for 3pter-p25 deletion syndrome and Pallister-Killian syndrome in NIPT-plus

目的探讨1例由扩展性无创产前检测(NIPT-plus)提示3pter-p25缺失综合征和Pallister-Killian综合征(PKS)高风险胎儿的遗传学病因。方法选取2023年6月27日于乌鲁木齐市妇幼保健院NIPT-plus检测提示3pter-p25缺失综合征和PKS高风险的1例胎儿为研究对象。采集孕妇相关临床资料,对胎儿羊水样本进行羊水染色体G显带核型分析与染色体微阵列分析(CMA),对其父母进行外周血染色体G显带核型分析,孕妇经遗传咨询后引产并对引产胎儿组织进行拷贝数变异测序(CNV-seq)。结果孕妇年龄为36岁,G3P1,因胎儿超声提示“胎儿双侧侧脑室对称、宽12 mm,未见明显胎儿透明隔腔,胎儿单脐动脉”就诊。CMA检测结果提示arr[GRCh37]3p26.3p26.1(61892_7439472)x1,12p13.33p12.2(173787_20064689)x3,缺失和重复片段大小分别为7.2 Mb和19.89 Mb,羊水的染色体核型分析结果为46,Xn,der(3)t(3;12)(p26;p12).arr;胎儿母亲的外周血染色体核型为46,XX,t(3;12)(p26;p12),胎儿父亲的外周血染色体核型正常。引产胎儿组织CNV-seq结果为seq[hg19]del(3)(p26.3p26.1)chr3:g.60000_7420000del,dup(12)(p13.33p12.2)chr12:g.60000_20020000dup,缺失和重复片段大小为7.36 Mb和19.96Mb,与CMA检测结果相符。结论该胎儿同时存在3p26.3p26.1微缺失及12p13.33p12.2微重复变异,根据其母亲染色体核型结果,推测胎儿的染色体变异源自母亲的不平衡配子。应用G显带核型分析与CMA检测技术可诊断胎儿染色体结构异常的类型及来源,从而明确胎儿的遗传学病因。

Objective Exploring the genetic etiology of a high-risk fetus with 3pter-p25 deletion syndrome and Pallister-Killian syndrome suggested by extended noninvasive prenatal testing(NIPT-plus).Methods In a case of a fetus with high risk of 3pter-p25 deletion syndrome and Pallister-Killian syndrome detected by NIPT-PLUS in Urumqi Maternal and Child Health Hospital on June 27,2023,we collected clinical information from the pregnant woman and performed G-banding chromosome karyotyping and chromosome microarray analysis(CMA)of fetal amniotic fluid,and fetal parents underwent peripheral blood G-banding chromosome karyotyping.Copy number variant sequencing(CNV-Seq)was performed on aborted tissue after the pregnant woman decided to induce labor.Results The pregnant woman was 36 years old,G3P1,fetal ultrasonography revealed symmetrical bilateral lateral ventricles that were 12 mm wide;there was no obvious septum pellucidum;and the fetus had a single umbilical artery.The result of CMA was arr[GRCh37]3p26.3p26.1(61892-7439472)x1,12p13.33p 12.2(173787-20064689)x3.The sizes of the deletion and duplication fragments were 7.20 Mb and 19.89 Mb,respectively.Karyotyping of the amniotic fluid identified the presence of a derivative chromosome 3 with the rearrangement t(3;12)(p26;p12).The peripheral blood karyotype of the pregnant woman was 46,XX,t(3;12)(p26;p12),while that of the father was normal.The CNV-seq results of induced foetal tissue were seq[hg19]del(3)(p26.3p26.1)chr3:g.60000_7420000del,dup(12)(p13.33p12.2)chr12:g.60000_20020000dup.The deleted and duplicated fragments were 7.36 Mb and 19.96 Mb respectively.which was consistent with the result of the CMA.Conclusion The fetus carried both a 3p26.3p26.1 microdeletion and a 12p13.33p12.2 microduplication variant,based on the results of its mother's chromosomal karyotype,it was hypothesized that the chromosomal variant originated from the mother's unbalanced gametes.The application of G-banding karyotyping and CMA can determine the type and origin of fetal chromosomal structural abnormalities.