应用单核苷酸多态性微阵列技术检测胎儿染色体6p25缺失综合征

Application of single nucleotide polymorphism microarray technique to detect fetal chromosomal 6p25 deletion syndrome

目的探讨染色体6p25缺失综合征的遗传学病因、临床表型和致病基因,结合文献探讨单核苷酸多态性微阵列(single nucleotide polymorphism microarray,SNP-array)检测技术在胎儿6p25缺失综合征产前诊断中的应用。方法羊膜腔穿刺取胎儿羊水,羊水细胞提取核酸后采用SNP-array对胎儿DNA进行全基因组扫描后分析基因组拷贝数变异,同时进行羊水G显带染色体核型分析。结果胎儿的6号染色体6p25.3-p25.2区域发生缺失,缺失片段大小约2.7Mb,包含已知的FOXC1、FOXF2、DUSP22、IRF4、EXOC2等15个OMIM基因,该片段缺失可导致6p25缺失综合征。羊水G显带染色体核型分析提示为46,XN,未见明显异常。结论染色体6p25.3-p25.2区域缺失可导致6p25缺失综合征,单倍剂量不足基因FOXC1在6p25缺失综合征中发挥关键作用。SNP-array检测技术分辨率高、准确性好,可以弥补染色体核型分析分辨率的不足,适用于胎儿6p25缺失综合征的产前诊断,可以为临床遗传咨询医生提供详细的诊断信息和再生育咨询参考。

Objective To explore the genetic causes of chromosome 6p25 deletion syndrome,clinical phenotype and disease genes.And discuss the application of single nucleotide polymorphisms microarray detection technology in 6p25 deletion syndrome prenatal diagnosis combined with the literature review.Method Fetal amniotic fluid sample was extracted by amniotic cavity puncture.Genome copy number variation of fetus DNA was analyzed by SNP-array genome-wide scan after amniotic fluid cell culture and G banding karyotype analysis was determined.Results There is a deletion fragment at 6p25.3-p25.2 region in fetus chromosome 6 and the fragment size is 2.7Mb.It contains some known OMIM genes,for example,FOXC1、FOXF2、DUSP22、IRF4 and EXOC2.The deletion of this region has highly correlated with clinical phenotype of 6p25 deletion syndrome.G banding karyotype of amniotic fluid sample result is 46,XN,no obvious abnormalities.Conclusions The deletion at 6p25.3-p25.2 region of chromosome 6 could result in 6p25 deletion syndrome.It may be associated with inadequate expression dose of FOXC1 gene.SNP-array detection technology has high resolution and accuracy,so it can make up for the resolution inadequacy of karyotype analysis.SNP-array detection technology may apply to the prenatal diagnosis of fetal 6p25 deletion syndrome.It Can provide detailed diagnostic information for clinical genetic consult and fertility consulting reference.