摘要目的 探讨全基因组高分辨染色体微阵列分析(chromosome microarray analysis,CMA)技术在产前超声或磁共振提示侧脑室扩张(ventriculomegaly,VM)且染色体核型为正常的胎儿中的应用价值.方法 收集2011年7月至2016年6月在广州市妇女儿童医疗中心产前诊断中心就诊的341例产前超声或磁共振提示胎儿为VM的孕妇病例,按VM的程度、是否合并其他异常、VM为单侧还是双侧以及孕妇是否高龄等因素进行多维度分组.对所有胎儿样本进行染色体核型分析,对染色体核型正常的胎儿样本进行CMA分析,并对全部病例进行临床随访,了解妊娠结局和新生儿预后.结果 (1)341例胎儿样本中,21例为染色体核型异常,异常核型发生率为6.2％(21/341).320例染色体核型正常,其中有179例(55.9％,179/320)胎儿样本进一步接受全基因组高分辨CMA检测,结果提示12例(6.7％,12/179)胎儿存在致病性拷贝数变异(copy number variations,CNVs).致病性CNVs大小范围在198 kb～8.71 Mb之间,分别为1q21.3q23.1微缺失、2q37.3微缺失、3p14.1p13微缺失、6q25.3微缺失、8q11.23微重复、10q21.1微缺失、15q11.2微缺失、16p13.11p12.3微重复、22q13.33微重复、22q11.21微重复(22q11微重复综合征)以及Xp21.1微缺失(Duchenne型肌营养不良症).(2)将VM胎儿的致病性CNVs检出率进行分组比较,轻度VM组和重度VM组分别为7.5％ vs.3.1％(P=0.615);孤立性VM组和非孤立性VM组分别为6.1％ vs.7.4％(P=0.732);单侧VM组和双侧VM组致病性CNVs检出率分别为5.6％ vs.7.9％(P=0.511);高龄组和非高龄组分别为6.7％ vs.6.7％(P=1.000).结论 VM胎儿中染色体核型异常检出率为6.2％.在染色体核型正常的VM胎儿中,CMA能额外提高6.7％的致病性检出率,且不同组别的VM与致病性CNVs之间的相关性无统计学意义.对于VM的胎儿建议进一步行CMA分析.

abstractsObjective To assess the value of genome-wide high-resolution chromosomal microarray analysis (CMA) for the delineation of pathogenesis for fetal ventriculomegaly diagnosed by ultrasound or magnetic resonance imaging (MRI).Methods Three hundred forty one cases of fetal ventriculomegaly were collected.The samples were grouped based on the extent of lateral ventricular dilatation,presence of additional features,site of occurrence,and the maternal age.All samples were subjected to karyotyping analysis.For those with a normal karyotype,DNA was extracted and hybridized with an Affymetrix CytoScan HD array.All cases were followed up.Results Among the 341 fetuses,21 (6.2％) were detected with an abnormal karyotype.For the 320 cases with a normal karyotype,179 (55.9％) have accepted CMA analysis.Potentially pathogenic CNVs were identified in 12 (6.7％) of the 179 cases,whose sizes ranged from 198 kb to 8.71 Mb.These included a 1q21.3q23.1 deletion,a 2q37.3 deletion,a 3p14.1p13 deletion,a 6q25.3 deletion,a 8q11.23 duplication,a 10q21.1 deletion,a 15q11.2 deletion and a 16p13.11p12.3 duplication,a 22q13.33 duplication,a 22q11.21 duplication and a Xp21.1 duplication (Duchenne muscular dystrophy).Pathogenic CNVs were detected respectively in 7.5 ％ and 3.1 ％ of those with mild and severe ventriculomegaly (P=0.615),in 6.1％ and 7.4％ of those with isolated and nonisolated ventriculomegaly (P =0.732),in 5.6％ and 7.9％ of those with unilateral and bilateral ventriculomegaly (P=0.511),and in 6.7 ％ of both elderly and non-elderly groups (P=1.000).Conclusion The detection rate for abnormal karyotypes among fetuses with ventriculomegaly was 6.2％.CMA can increase the detection rate by approximately 6.7％.There was no significant correlation between ventriculomegaly and presence of pathogenic CNVs.In clinical practice,fetuses with ventriculomegaly and a normal karyotype should be considered for CMA analysis.