Copy number variations characterization and possible candidate genes in miscarriage and stillbirth by next-generation sequencing analysis.

Abstract

OBJECTIVE\nTo explore the etiological relationship between miscarriage and stillbirth and copy number variations (CNVs), and to provide useful genetic guidance for high-risk pregnancy.\n\n\nMETHODS\n659 fetal samples were recruited and subjected to DNA extraction and CNV sequencing (CNV-Seq), relevant medical records were collected.\n\n\nRESULTS\nThere were 322 cases (48.86%) with chromosomal abnormalities, including 230 with numerical abnormalities, 92 with structural abnormalities. Chromosomal monosomy variations mainly occurred on sex chromosomes, and trisomy variations mainly occurred on chromosomes 16, 22, 21, 18, 13, and 15. 41 pathogenic CNVs (23 microdeletions and 18 microduplications) were detected in 27 fetal tissues. The rates of numerical chromosomal abnormalities were 29.30% (109/372), 32.39% (57/176) and 57.66% (64/111) in <30-year old, 30-34-year old, and ≥35-year old age pregnant women, respectively, increased with the increasing age (P<0.001). There was statistically significant difference (χ2 =7.595, P=0.022) in the rates of structural chromosomal abnormalities in these groups (13.71%, 18.75% and 7.21%, respectively). The rates of numerical chromosomal abnormalities were 45.44% (219/482), 7.80% (11/141) and 0% (0/36) in ≤13 gestational weeks, 14-27 weeks, and ≥28 weeks groups, respectively, decreased with the increasing gestational week of fetuses (P<0.001).\n\n\nCONCLUSION\nSome useful and accurate genetic etiology information has been obtained, it provides useful genetic guidance for high-risk pregnancy.