应用SNParray诊断一例5p缺失综合征合并11q部分三体胎儿

Improved identification for 5p deletion syndrome and partial trisomy llq presented in a fetus by SNP array

目的探讨单核苷酸多态性微阵列（single nucleotide polymorphism array,SNP array）在胎儿5p缺失综合征合并11q部分三体诊断中的应用。方法对1例多发畸形胎儿行羊水G显带核型分析及SNParray分析，以明确染色体异常情况。胎儿父母行外周血G显带核型分析以确定胎儿异常染色体的来源，荧光原位杂交（fluorescence in situ hybridization, FISH）检测验证核型分析的结果。结果羊水细胞G显带核型分析显示胎儿核型为46，XY，der（5）（？：：p15→qter）。SNParray分析结果显示胎儿5p15．33p15．2（chr5：113576—14020561）缺失，大小为13．907Mb，缺失区域与5p缺失综合征区域重叠；11q23．3q25（chr11：116684627-134938470）重复，大小为18．254Mb，未覆盖已知的疾病综合征。胎儿母亲染色体核型为46，XX；胎儿父亲染色体核型为46，XY，t（5；11）（p15；q23）。父亲外周血中期分裂相三色FISH结果验证了5p和11q相互易位。结论SNParray可以鉴别G显带无法完全辨别的胎儿5p缺失综合征合并11q部分三体，并精确定位断裂点，从而促进表型相关的关键区域定位和候选致病基因的筛选和鉴定，为基因型和表型的关系分析积累数据。

Objective To investigate the prenatal application of single nucleotide polymorphism array （SNP array） in the identification of 5p deletion syndrome with partial trisomy 11q. Methods G-banded karyotyping and SNP array were performed using amniocytes on a fetus with multiple malformations for the identification of chromosome abnormality. Furthermore, karyotyping was carried out on the parental peripheral blood specimens to ascertain the origin of chromosome abnormalities and then fluorescence in situ hybridization （FISH） was also utilized to confirm the results. Results Karyotype of amniocyte showed 46, XY, der（5） （？ ：：p15→qter）. SNP array revealed a 13. 907 Mb deletion at 5p15.33p15.2 （chr5：113 576- 14 020 561） , overlapping the region of 5p deletion syndrome, and a 18. 254 Mb duplication at 11q23.3 q25 （chr11：116 684 627-134 938 470）, overlapping no known syndrome. Karyotype of the parents showed a normal 46, XX in mother and 46, XY, t（5;11）（p15 ;q23） in father. Three-color metaphase FISH analysis on paternal peripheral blood specimens also confirmed the paternal karyotyping result. Conclusion SNP array could uncover 5p deletion syndrome with partial trisomy llq unidentified by G-banded karyotyping and accurately locate the genomic breakpoints, facilitating the mapping of pathogenic critical regions and the identification of candidate genes, also accumulating research data for genotype-phenotype study.