一例9号微小额外标记染色体的遗传学分析

Genetic analysis of a case with a supernumerary marker derived from chromosome 9

目的:结合细胞遗传学与分子遗传学技术探讨一例9号染色体微小额外标记染色体(small supernumerary marker chromosome,sSMC)的遗传学机制。方法:因超声发现一例胎儿左心室点状强回声,无创产前检测提示胎儿8号单体或部分缺失、9号三体、11号单体或部分缺失高风险,对孕中期血清学筛查提示单项中值倍数值异常的孕妇进行羊水穿刺,进行染色体G显带核型分析及单核苷酸多态性微阵列(single nucleotide polymorphism array,SNP array)检测。对孕妇进一步进行C显带核型分析和荧光原位杂交(fluorescence in situ hybridization,FISH)检测。结果:孕妇染色体G显带核型为47,XX,+mar[20]/46,XX[80],C显带显示sSMC中间深染,提示为着丝粒区域,两端浅染,提示含有常染色质;采用9pter/9qter探针的FISH结合DAPI显带分析结果显示孕妇为47,XX,+mar.ish i(9)(9p10)(9p++)[2]/46,XX[18];SNP array提示孕妇染色体9p24.3q13区存在68.1 Mb的重复,检索数据库提示该重复片段致病可能性大。胎儿及配偶的染色体核型和SNP array检测均未见异常。结论:结合细胞遗传学和分子遗传学技术分析了一例9号染色体sSMC的遗传学机制,有助于了解了这类异常染色体的再发风险。

Objective To delineate a small supernumerary marker chromosome(sSMC)derived from chromosome 9 with combined cytogenetic and molecular methods.Methods For a pregnant woman with fetal ultrasound revealing left ventricular punctate hyperechoic echo,and a high risk for monosomy or partial deletion of chromosome 8,chromosome 9 trisomy,monosomy or partial deletion of chromosome 11 by non-invasive prenatal testing,and an abnormal MoM value revealed by mid-term serum screening,amniocentesis was performed for G banded chromosomal analysis and single nucleotide polymorphism array(SNP-array)assay.Peripheral blood samples of the woman and her spouse were also collected for the above tests.In addition,the woman was further subjected to C banding karyotyping analysis and fluorescence in situ hybridization(FISH)assay.Results The G-banded karyotype of the pregnant women was 47,XX,+mar[20]/46,XX[80],whilst C-banding analysis showed a deep stain in the middle of the sSMC(suggestive of centromeric region)and light stain at both ends(suggestive of euchromatism).FISH combined with DAPI banding analysis using 9pter/9qter probes revealed a karyotype of 47,XX,+mar.ish i(9)(9p10)(9p++)[2]/46,XX[18],whilst SNP-array has revealed a 68.1 Mb duplication in the 9p24.3q13 region.A database search has suggested the duplication to be likely pathogenic.No abnormality was found in her fetus and spouse by karyotyping and SNP-array analysis.Conclusion Through combined cytogenetic and molecular genetic analysis,a sSMC derived from chromosome 9 was delineated,which has enabled genetic counseling for the couple.