Application of Array-based Comparative Genomic Hybridization in the Prenatal Diagnosis of Fetal Chromosomal Aberration in Gravidas with Advanced Age

  Objective  To evaluate the clinical application of array-based comparative genomic hybridization (a-CGH) in the prenatal diagnosis of fetal chromosomal aberrations in gravidas with advanced maternal age (AMA).

  Methods  A total of 3 677 amniotic fluid samples from pregnant women who underwent amniocentesis for prenatal diagnosis solely due to AMA were selected. Array-CGH was performed on the Agilent CGX^TM (8X60K) platform and the data were analyzed by the Genoglyphix software.

  Results  The overall detection rate of chromosomal aberration was 2.04% (75/3677), with 53.33% (40/75) being aneuploidies, including 22 cases of trisomy-21, 5 cases of trisomy-18, 8 cases with XXY, 3 cases of XYY and 2 cases of mosaic monosomy X, 32.00% (24/75) being pathogenic copy number variations (pCNVs), including 19 cases of microdeletion and 5 cases of microduplication, with the fragment size ranging from 323 kb to 26 780 kb, and 14.67% (11/75) being likely pathogenic CNVs (lpCNVs), including 7 cases of microdeletion and 7 cases of microduplication, with the fragment size ranging from 358 kb to 16 873 kb. Besides, the detection rate of CNVs of unknown clinical significance (VUS) was 0.84% (31/3 677). The detection rate of aneuploidies increased significantly with increased maternal age (P<0.05). However, there were no significant differences in the detection rate of p/lpCNVs among different maternal age groups (P>0.05).

  Conclusion  Our findings suggest that, compared with traditional karyotype analysis, a-CGH not only detects aneuploidies, but also detect pathogenic CNVs, including microdeletion/microduplication syndromes. The detection rate of fetal aneuploidies was closely correlated to maternal age. However, no correlation was found between the detection rate of p/lpCNVs and maternal age.