Xq26.2缺失122 kb致Simpson-Golabi-Behmel综合征Ⅰ型胎儿的产前诊断及遗传学分析  

Prenatal diagnosis and genetic analysis of a fetus affected with Simpsone-Golabie-Behmel syndrome type 1 due to a 122 kb Xq26.2 deletion

作　　者：何凤娟 朱红岩 张春艳 毛秀珍 HE Fengjuan;ZHU Hongyan;ZHANG Chunyan;MAO Xiuzhen(Prenatal Diagnostic Center,Jiangsu Province(Suqian)Hospital,Suqian First Hospital,Suqian,Jiangsu 223800,China)

机构地区：[1]江苏省人民医院宿迁医院/宿迁市第一人民医院产前诊断中心,江苏宿迁223800

出　　处：《中国优生与遗传杂志》2024年第8期1667-1672,共6页Chinese Journal of Birth Health & Heredity

基　　金：宿迁市科技计划资助项目(K202212);宿迁市“宿迁英才”群英计划青年资助项目([2022]QNXM-0050)。

摘　　要：目的对1例Simpson-Golabi-Behmel综合征Ⅰ型(SGBS1)胎儿进行孕期临床表型和遗传学分析,明确该综合征的遗传学病因和孕期的临床表型,为该综合征进行产前诊断提供依据。方法采集胎儿的羊水及其父母的外周血样本,对胎儿进行羊水脱落细胞培养及核型分析,对胎儿羊水样本排除母源污染并确认生物学父母关系,应用家系全外显子组测序(WES)进行拷贝数变异分析和单基因位点变异分析。结果WES提示其Xq26.2区存在122kb(chrX:132548804-132670349)的半合子缺失,为新发变异,该区域覆盖磷脂酰肌醇蛋白聚糖4(GPC4#300168)、磷脂酰肌醇蛋白聚糖3(GPC3#300037)两个OMIM基因的部分外显子区域,其中GPC3基因可能与X染色体连锁的SGBS1有关。短串联重复序列分析结果显示胎儿父母确为其生物学父母。分析孕期超声检测的综合孕周,发现该患儿的宫内生长过度在24周后才能检测到略微增大,在后续的生长发育中超声孕周与实际孕周差距逐步增大。结论应用WES检测并通过qPCR验证相关区域确诊该胎儿的致病原因为新发的Xq26.2微缺失;孕中后期胎儿测量孕周超过实际孕周,且差距持续增大,合并面部异常和内脏的异常肿大可能是SGBS1胎儿产前超声的重要指标。产前遗传咨询可结合该表型进行遗传学诊断,充分告知症状和预后情况,在孕妇自愿和知情下进行优生选择。Objective To identify the clinical phenotype and genetic analysis of a fetus with Simpson-Golabi-Behmel syndrome(SGBS)type 1 during pregnancy,analyze the relationship between the genetic etiology and the clinical phenotype during pregnancy by phenotype and gene analysis,and provide reference for diagnosis.Methods Fetus amniotic fluid and peripheral blood samples of its parents were collected.The fetus was subjected to chromosomal karyotyping,whilst the fetus and its parents were subjected to whole exon sequence.The candidate copy number variation and single nucleotide polymorphism were analyzed.Results WES indicated that it has carried a novel 122 kb deletion at Xq26.2,which is associated with hereditary Glypican 4(GPC4 OMIM#300168)and Glypican 3(GPC3 OMIM#300037),in which the GPC3 gene may be associated with X-linked SGBS1.Parental relationship was confirmed between the fetus and its parents.Following genetic counseling,the parents has chosen to terminate the pregnancy.By analyzing the comprehensive gestational weeks of ultrasound detection during pregnancy,it was found that the intrauterine growth transition of this child could not be detected until 24 weeks,and the gap between the gestational age of ultrasound and the actual gestational age gradually increased in the subsequent growth and development.Conclusion WES and qPCR can effectively detect Xq26.2 de novo microdeletion.The clinical manifestations of this syndrome mainly include facial abnormalities,abnormal enlargement of internal organs and the measured gestational age in the second and third trimesters of pregnancy exceeds the actual gestational age,and the gap continues to increase.Upon prenatal consultation,the prognosis of the fetus should be fully informed,and advice should be provided in combination with the preference of the couple,pregnancy history,family condition and other aspects.

关 键 词：Xq26.2微缺失综合征 磷脂酰肌醇蛋白聚糖3基因 磷脂酰肌醇蛋白聚糖4基因 产前超声 Simpson-Golabi-Behmel综合征Ⅰ型 

分 类 号：R714.5[医药卫生—妇产科学]