Objective：This study aims to establish a rapid and simple method for prenatal diagnosis of single gene disorders related to skeletal dysplasia by PCR amplification using amniotic fluid. Methods：Thirty eight fetuses with bone dysplasia diagnosed by ultrasound from April 2013 to January 2018 were carried out amniocentesis combined with diagnosis of single gene disorders of achondroplasia，hypochondroplasia，thanatophoric dysplasia and osteogenesis imperfecta in First Affiliated Hospital of Nanjing Medical University. Amniotic fluid extracted from pregnant women was added to PCR buffer containing neutral salt and other substances without fetal cell culture or extraction of DNA. The pH value of buffer was controlled at 8-10. The target fragments of FGFR3 and COL1A2 genes was amplified by directly adding 8 μL of amniotic fluid to the reaction mixture of PCR amplification and followed by sequencing to perform prenatal diagnosis. The effect of components in reaction mixture on amplification efficiency in the method was investigated. Results：In 38 cases of fetal samples，3 cases of thanatophoric dysplasia（including 1 case of type Ⅰ and 2 cases of type Ⅱ），3 cases of achondroplasia and 1 case of hypochondroplasia were detected. The best amplification efficiency was obtained by using neutral salt buffer，0.20 U/μL Promega Taq DNA polymerase and 1.2 pmol/μL each primer. Conclusion：This method omits the two tedious steps，which were amniotic fluid cell culture and extraction of fetal DNA from amniotic fluid. Furthermore，amplification can be carried out directly without concentration of amniotic fluid. The method shortens the time of diagnosis，saves the cost of diagnosis，and further reduces the possible cross contamination of samples in PCR processes. It will be a promising，rapid，and efficient tool for prenatal gene diagnosis.