胎儿唇腭裂全基因组拷贝数变异意义的研究

Application of chromosome microarray analysis for the delineation of pathogenesis of fetal cleft lip/palate

目的探讨染色体微阵列分析(CMA)技术在产前超声提示胎儿唇腭裂的遗传学病因诊断中的应用价值。方法收集2014年1月至2017年12月在广州市妇女儿童医疗中心产前诊断中心就诊孕妇超声提示胎儿唇腭裂病例100例,对胎儿羊水及脐带血进行CMA并应用ChAS软件和相关生物信息学数据库对结果进行判断。结果在100例胎儿唇腭裂样本中,致病性拷贝数变异(CNVs)检出12例(12/100),分别为16p11微重复综合征、18q缺失综合征、Wolf-Hirschhorn综合征、22q11远端缺失综合征和22q11微缺失综合征等遗传综合征;不确定性CNVs(VOUS)检出率为7.0%(7/100),单纯性唇裂胎儿中未检出致病性CNVs,唇裂合并腭裂胎儿致病性CNVs检出率为9.1%(5/55),综合征性唇腭裂为33.3%(7/21)。结论 CMA技术在唇腭裂疾病病因诊断中具有显著的应用价值,建议对唇腭裂胎儿进行基因芯片检查进行产前诊断。

Objective To assess the value of genome-wide high-resolution chromosomal microarray analysis(CMA)for the delineation of pathogenesis of fetal Cleft lip/palate diagnosed by ultrasound.Methods 100 cases of fetal cleft lip/palate were collected.All samples were subject to karyotyping analysis,and DNA was extracted and hybridized with an Affymetrix CytoScan HD array.The data was analyzed by the ChAS,Decipher and other data banks.Results Potentially pathogenic CNVs were identified in 12(12.0%)of the 100 cases.These included the 16 p11 duplication,18 q deletion,WHS,22 q11 distal deletion and 22 q11 deletion syndromes.VOUs were detected at a percentage of 7.0%(7/100).No cases with isolated cleft lip had the pathogenic CNVs.Pathogenic CNVs were detected at a percentage of 9.1%(5/55)and 33.3%(7/21),respectively,of those with Cleft lip and palate and syndromes’cases.Conclusion There was a significant correlation between cleft lip/palate and presence of pathogenic CNVs.In clinical practice,fetuses with cleft lip/palate should be considered for CMA analysis.