Abstract: Objective To analyze the causes of oligohydramnios in the second trimester using gene chip technology and whole exon detection technology. Methods Fifteen cases with oligohydramnios in the middle trimester of pregnancy admitted to our hospital from September 2015 to December 2017 were enrolled in our study. Then chromosomal microarray analysis (CMA) and / or Whole exome sequencing (WES) were applied to fi nd out suspected gene mutation sites. Results Fifteen fetuses were examined by CMA and no abnormalities was found. WES was applied in 12 fetuses, and 10 cases had no suspicious genes, while 2 cases had suspicious genes. Of the 2 cases, 1 case had ACE gene c.1631T> C (p.L544P) and c.3070-3071delCT (p.L1024Lfs*17) complex heterozygous mutation, and its related disease was renal tubule dysplasia (RTD); 1 case had ANKS6 c.2394+1G> A (IVS13), c.621 (Exon2) _c.622 (Exon2) insTGGTG complex heterozygosity, and its related disease was type 16 of renal wasting disease (Nephronophthisis-16, NPHP16). Conclusion There is no correlation between duplication of chromosome microdeletion and oligohydramnios in the middle trimester of pregnancy, and CMA is unnecessary in the middle period of pregnancy when oligohydramnios is found.Oligohydramnios in the middle of pregnancy may be caused by autosomal recessive hereditary disease, and exon detection is helpful in clarify the disease causes and guiding repregnancy.