一例18号染色体短臂部分四体胎儿的遗传学分析

Genetic analysis of a fetus with partial 18p tetraploidy syndrome

目的对1例心脏超声异常胎儿进行遗传学诊断及分析，探讨其染色体变异与表型的关系。方法使用常规G显带法对胎儿脐带血淋巴细胞染色体核型进行初步分析，同时用短串联重复序列荧光定量PCR（short tanderm repeats quantitative fluorescence PCR，STR-QF-PCR）法快速分析胎儿DNA作为辅助检查，再采用全基因组低覆盖度测序法（whole genome low coverage sequencing，WGS）检测染色体非整倍体100kb以上的缺失／重复以明确诊断。结果该胎儿染色体常规G显带分析核型为47，XN，＋mar。脐带血DNA的STR-QF-PCR检测发现其18号染色体GATA178F11基因座的拷贝数为4，重复片段来源于母亲。WGS法检测胎儿DNA结果为46，XN，dup（18p11．21p11．32）．seq[GRCh37／hg19]（10001-15378887）×4，重复片段长约15．38Mb。结论该胎儿的先天性心脏病可能与其18号染色体短臂部分重复有关，合理运用细胞遗传学和分子遗传学检测方法有助于对异常胎儿遗传学变异进行明确诊断。

Objective To analyze a fetus with abnormal cardiac ultrasound by using various techniques and explore its genotype-phenotype correlation. Methods Lymphocytes derived from umbihcal cord blood sample were subjected to G-banding analysis. Short tandem repeats quantitative fluorescence PCR （STR- QF-PCR） was used for analysis of fetal DNA as an auxiliary test. Low-coverage whole genome sequencing （WGS） was used to detect chromosomal deletion/duplication which exceeded 100 kb in size. Results The karyotype of the fetus was 47 ,XN, ＋mar. As detected by STR-QF-PCR, the copy number of GATA178F11 locus on chromosome 18 was 4, and the duplicated fragment was derived from the mother. WGS suggested that the fetus to be46,XN,dup（18p11.21p11.32）.seq[GRCh37/hg19] （10 001 - 15 378 887）× 4, with the duplicated fragment spanning approximately 15.38 Mb. Conclusion The cardiac malformation of the fetus may be attributed to the partial duplication of chromosome 18p. Combined cytogenetic and molecular methods can facilitate prenatal detection of genetic abnormalities.