应用单核苷酸多态芯片技术产前诊断四例胎儿新发染色体变异

Analysis of four fetuses with de novo chromosomal rearrangments using single nucleotide polymorphism microarray chips

目的探讨单核苷酸多态性芯片（single nucleotide polymorphisms array，SNP—array）技术在新发染色体变异产前诊断中的应用价值。方法选取产前诊断G显带染色体核型为新发平衡易位或微小额外标记染色体的4名孕妇，知情同意抽取胎儿脐带血DNA，按照标准的微阵列操作手册进行杂交、洗涤及全基因组扫描，扫描数据通过相应的计算机软件进行分析。结果例1未发现致病性拷贝数改变；例2嵌合的微小额外标记染色体来源于4号染色体，包含约9Mb的重复；例3除了遗传了来源于母亲的两条平衡易位染色体，还出现了两条新发的易位染色体，但SNP-array未发现致病性拷贝数改变；例4的G显带显示的两条“平衡”易位染色体实为不平衡畸变：1号染色体25Mb的重复和9号染色体17Mb的缺失。例1和例3出生后随访智力体格发育均未见异常。结论SNP-array能够在DNA水平上甄别胎儿新发“平衡”易位或微小额外标记染色体的致病性，在产前诊断中不失为传统染色体核型分析的重要补充。

Objective To assess the value of single nucleotide polymophism （SNP） microarray for delineation of de novo chromosomal rearrangements detected upon prenatal diagnosis. Methods SNP microarray analysis was carried out for 4 fetuses with de novo sSMCs or balanced reciprocal translocations. Genomie DNA was extracted from cord blood samples, and amplified, tagged and hybridized following the manufacturer＇s protocol. Data were collected and analyzed. Results No pathogenic CNVs were detected in fetus A, whose sSMCs was verified to be heterochromatin. Fetus B, who had a de novo mosaic sSMCs, was found to have a 9 Mb duplication in 4p12-q13 which is associated with speech delay and mental retardation. No pathogenic CNVs were detected in fetus C who has 2 translocation chromosomes inherited from its mother and 2 chromosomes derived from a de novo translocation. Fetus D, who had a de novo ＂balanced＂ reciprocal translocation, was found to have a 25 Mb duplication in lq25 and a 17 Mb deletion in 9p22. Cases A and C had normal physical and mental evaluation after birth. Conclusion For its ability to detect cryptic imbalance in de novo sSMCs or balanced reciprocal translocations, SNP-array has provided a powerful aid to conventional karyotype analysis during prenatal diagnosis.