胎儿羊水额外小标记染色体的细胞及分子遗传学分析

Cytogenetic and molecular genetic analysis of small supernumerary marker chromosomes in fetal amniotic fluid

目的了解胎儿羊水额外小标记染色体（small supernumerary marker chromosomes，sSMC）的来源，探讨其发生机理并为临床遗传咨询提供参考。方法应用常规G显带分析2例胎儿羊水细胞的染色体核型及其直系亲属的外周血染色体核型，用高通量全基因组测序技术明确胎儿sSMC的片段来源和区域。结果1号胎儿羊水的染色体核型分析结果为47，XY，4-mar，FISH检测结果正常，胎儿超声检查无异常；胎儿父亲外周血染色体核型47，XY，＋mar，FISH检测结果正常，临床表型、智力正常；胎儿及其父亲高通量全基因组测序结果为46，XY，dup（21）（q11．2；q21．1），21号染色体长臂14．6～20．8Mb位置重复，长约6．2Mb。胎儿活产临床表型无异常，发育良好；胎儿祖母外周血染色体核型46，XX，t（15；21）（q13；p13），FISH检测结果正常，临床表型、智力正常；胎儿母亲、祖父外周血染色体正常。2号胎儿羊水染色体核型分析结果为47，XX，＋mar，FISH检测结果正常，高通量全基因组测序结果为46，XX，胎儿活产临床表型无异常，发育良好。胎儿父母外周血染色体核型正常。结论由于sSMC来源的多样性，其鉴定需要在传统的显带核型分析基础上，结合高通量全基因组测序技术，精确定位异常染色体来源和区域，为产前诊断和遗传咨询提供参考。

Objective To explore the origin and mechanism of small supernumerary marker chromosomes （sSMC） in order to facilitate genetic counseling. Methods Chromosome karyotypes of two fetuses and their immediate family members were analyzed by conventional G banding. High-throughput whole genome sequencing was used to determine the origin of sSMCs. Results Fetus 1 was shown to have a karyotype of 47, XY, ＋mar but with normal FISH and B ultrasound findings. Its father also had a 47, XY, ^-mar karyotype with normal FISH results and clinical phenotype. High-throughput genome sequencing revealed that fetus 1 and its father were both 46,XY,dup（21）（q11. 2;q1.1） with a 6.2 Mb duplication of the long arm of chromosome 21. The fetus was born with normal phenotype and developed well. Its grandmother also had a karyotype of 46,XX, t（15; 21）（q13; p13） with normal FISH result and clinical phenotype. The karyotypes of its mother and grandfather were both normal. Analysis of fetus 2 showed a 47 , XY, ＋ mar karyotype with normal FISH results. High-throughput genome sequencing suggested a molecular karyotype of 46, XX. The fetus was born with normal phenotype and developed well. The karyotypes of its parents were both normal. Conclusion Considering their variable origins, identification of sSMC should combine conventional G banding analyses with high-throughput whole genome sequencing for precise delineation of the chromosomes.