七例产前诊断的标记染色体及复杂染色体畸变的光谱核型分析

Spectral karyotyping of seven prenatally detected marker chromosomes and complex chromosome aberrations

目的探讨光谱核型分析（spectral karyotyping，SKY）结合荧光原位杂交（fluorescence in situ hybridization，FISH）及传统核型分析技术在产前诊断标记染色体及复杂染色体畸变中的应用。方法对产前诊断中常规G显带分析发现的5例标记染色体以及2例复杂染色体畸变的胎儿样本进行SKY分析，必要时应用FISH技术进一步鉴定或采用C显带、N显带技术进行辅助诊断，并分析胎儿产前超声检查、生后随访或病理解剖结果。结果5例标记染色体的病例中2例为大的标记染色体，3例为中等大小标记染色体；1例胎儿为父源性遗传，4例为新发突变。用SKY分析发现2例为非近端着丝粒来源（分别为4号、9号染色体），2例为近端着丝粒来源（分别来自22号、21号染色体），1例为X染色体来源。3例经FISH检查证实了SKY分析结果。5例标记染色体的胎儿4例终止妊娠，1例父源性遗传者足月分娩，生后随访1年未见异常。2例产前诊断为复杂染色体畸变的胎儿，其中1例经常规G显带分析为不明来源的衍生染色体，SKY诊断为8号染色体自身部分重复；另1例经SKY诊断为2号与6号染色体易位的胎儿足月分娩，随访6个月时有生长发育迟缓。结论应用SKY结合FISH及传统的核型分析可对产前诊断中难以确定来源的标记染色体及复杂染色体畸变作出诊断，结合超声波检查结果，可更好地为临床咨询提供指导。

Objective To perform spectral karyotyping （SKY）, fluorescence in situ hybridization （FISH） and conventional karyotyping on prenatally detected marker chromosomes and complex chromosomal aberrations. Methods Five marker chromosomes and 2 complex chromosome aberrations diagnosed by G banding were collected. SKY was performed to verify the composition of marker chromosomes. FISH was used to confirm the diagnosis when necessary. In certain cases, C or N banding technique was employed to verify the composition of chromosomes. Results of ultrasonography and pregnancy outcome were reviewed. Results Among the 5 marker chromosomes, 2 were large and 3 were medium in size, 4 were de novo and one was inherited from the father. By SKY analysis, 2 marker chromosomes have originated from non- acrocentric chromosomes （4 and 9）, whilst the other two have originated from acrocentric chromosomes （21 and 22）. The remainder was derived from X chromosome. The SKY results were confirmed by FISH in 3 cases. Four cases have chosen to terminate the pregnancy after genetic counseling. A fetus with inherited paternal marker chromosome was delivered at term, and showed normal development during the first year of life. As for the other 2 cases with complex chromosome aberrations, by SKY examination, one had duplication in chromosome 8 and the other had chromosome rearrangements derived from translocation between chromosomes 2 and 6. In the latter case the fetus was delivered at term but showed developmental retardation at 6 months. Conclusion SKY in combination with FISH can facilitate identification of the origins of marker chromosomes as well as complex chromosomal aberrations. With combined information from ultrasonography, SKY and FISH, effective counseling may be offered to the patients.