CNV-seq联合染色体核型分析在NT增厚胎儿遗传学诊断中的应用价值  

Application value of CNV-seq combined chromosome karyotype analysis in fetal genetic diagnosis of NT thickening

作　　者：王文芳 韩燕媚 陈宏健 叶婷婷[1] 付彬彬[1] 王惠卿 Wang Wenfang;Han Yanmei;Chen Hongjian;Ye Tingting;Fu Binbin;Wang Huiqing(Department of Medical Genetics,Haikou Maternal and Child Health Hospital,Haikou 570100,China;Department of Prenatal Diagnosis Center,Hainan Modern Women and Children’s Hospital,Haikou 571100,China)

机构地区：[1]海口市妇幼保健院医学遗传科,海口570100 [2]海南现代妇女儿童医院产前诊断中心,海口571100

出　　处：《国际遗传学杂志》2024年第2期79-85,共7页International Journal of Genetics

基　　金：海南省卫生计生行业科研项目(21A200074)。

摘　　要：目的探讨基因组拷贝数变异测序(copy number variation sequencing,CNV-seq)技术和染色体核型分析在颈项透明层(nuchal translucency,NT)增厚胎儿中的临床应用价值,分析胎儿NT增厚与染色体异常的关系。方法收集2021年1月至2022年12月在海口市妇幼保健院进行CNV-seq检测及核型分析的106例NT增厚胎儿的资料,根据胎儿NT厚度分为2.5~3.4 mm组(n=50),3.5~4.4 mm组(n=34),≥4.5 mm组(n=22),根据产前诊断指征分为孤立性NT增厚组(n=69)和非孤立性NT增厚组(n=37)。采用χ2检验或Fisher精确概率法对染色体异常分布情况及检出率进行分析。比较CNV-seq检测和染色体核型分析的遗传学诊断结果,随访妊娠结局。结果106例NT增厚胎儿,核型分析的染色体异常检出率为29.25%(31/106),其中染色体非整倍体18例,性染色体异常4例,染色体结构异常9例。CNV-seq的染色体异常检出率为42.45%(45/106),其中染色体非整倍体19例,性染色体异常4例,染色体结构异常22例;致病性CNV为31.13%,可能致病性CNV为2.83%,临床意义未明CNV为8.49%。CNV-seq对染色体异常检出率随NT值的增加而增加,差异有统计学意义(P=0.005)。核型分析和CNV-seq在非孤立性NT增厚胎儿染色体异常的检出率均明显高于孤立性NT增厚胎儿(均P<0.001)。核型正常的NT增厚胎儿,CNV-seq检出染色体异常14例;核型分析发现的罗氏易位型21-三体1例和平衡易位1例,CNV-seq则未能检出。CNV-seq联合核型分析对胎儿染色体异常的检出率高于染色体核型分析(P=0.023)。结论CNV-seq联合染色体核型分析能有效提高胎儿染色体异常的检出率,更有利于产前遗传学诊断。Objective To investigate the clinical application value of genome copy number variation sequencing(copy number variation sequencing,CNV-seq)and chromosome karyotype analysis in fetuses with nuchal transparent layer(nuchal translucency,NT)thickening,and to analyze the relationship between NT thickening and chromosome abnormalities.Methods Collect data of 106 fetuses with NT thickening were collected from January 2021 to December 2022 in Haikou Maternal and Child Health Hospital for CNV-seq detection and karyotype analysis.According to the fetal NT thickness,it is divided into 2.5~3.4 mm group(n=50),3.5~4.4 mm group(n=34),≥4.5 mm group(n=22).According to prenatal diagnostic indications,it is divided into isolated NT thickening group(n=69)and non isolated NT thickening group(n=37).Analyze the distribution and detection rate of chromosomal abnormalities using 2 test or Fisher’s exact probability method.Compare the genetic diagnosis results of CNV seq detection and chromosome karyotype analysis,and follow up the pregnancy outcomes.Results Among 106 cases of NT thickened fetuses,the detection rate of chromosomal abnormalities in karyotype analysis was 29.25%(31/106),including 18 cases of chromosomal aneuploidy,4 cases of sexual chromosomal abnormalities,and 9 cases of chromosomal structural abnormalities.The detection rate of chromosome abnormality in CNV-seq was 42.45%(45/106),including 19 cases of chromosome aneuploidy,4 cases of sex chromosome abnormality and 22 cases of chromosome structure abnormality.The pathogenic CNV was 31.13%,the probable pathogenic CNV was 2.83%,and the clinical significance was 8.49%.The detection rate of CNV-seq for chromosome abnormality increased with the increase of NT value,the difference was statistically significant(P=0.005).The detection rates of chromosomal abnormalities in non isolated NT thickened fetuses using karyotype analysis and CNV-seq were significantly higher than those in isolated NT thickened fetuses(P<0.001,respectively).Among NT thickened fetuses with normal karyo

关 键 词：颈项透明层 染色体核型分析 基因组拷贝数变异测序 染色体变异 

分 类 号：R714.5[医药卫生—妇产科学] R440[医药卫生—临床医学]