Gene mutation loci screening for fetal short limb anomalies. Published in Chinese Journal of Perinatal Medicine Lu Yanping Cheng Jing Wang Longxia Wang Shujuan Xiong Lihua Gao Zhiying Yuan Huijun Li Yali [Abstract] Objective To investigate the causative genetic wind mutation loci for fetal short limb malformation. Methods From August 2008 to August 2011, a total of lo cases of fetuses with apparent short limbs were detected by routine fetal ultrasonography at 18-24 weeks and/or 30-32 weeks of gestation. Amniotic fluid or umbilical cord blood was drawn for fetal karyotype analysis. Polymerase chain reaction and direct sequencing were used. The hotspot mutation sites of fibroblast growth factor receptor 3 (FGFR3) gene in amniotic fluid or cord blood were detected. Both parents of fetuses with chromosomal and FGFR3 gene detection abnormalities underwent sequencing of the same part of the FGFR3 gene. One fetal JL (case 3) had poor skull ossification. Insufficient chondrogenesis was considered. All exons of FGFR3 gene and SLC26A2, exons of Tripl1 gene were sequenced. The results: 10 fetuses with short limb malformation: 5 cases were detected in the middle and late gestation. The karyotype analysis revealed that one case was chimeric (46. XY/45, XY, I18). The remaining 9 cases were normal. 10 fetuses were tested for hotspot mutations in the FGFR3 gene at the umbrella and 4 mutations were found. One of them was a rare C.1108G>T (G370C) mutation. The gestational age was 2l “weeks. The diagnosis of lethal osteogenesis imperfecta was made; the other 3 cases were FGFR3 C.1138G>A(G380R) mutations in fetuses at 30-32 weeks of gestational age. Both parents of the four fetuses with the basal meat mutation had no mutations in the phase I locus. The risk of recurrence was low. In three of the cases, the mothers of the fetuses have now delivered again and the newborns have no abnormalities. All exons of FGFR3 gene and sLC26A2 and Tripl11 gene were detected in the fetuses of case 3. Conclusion The detection of chromosomal and FGFR3 base flashpoint mutation sites can clarify the teratogenic flesh for some fetuses with short limb malformation, and provide accurate genetic counseling and prenatal diagnosis for the affected families for re-pregnancy; the fetuses with obvious short limbs found by ultrasound in late pregnancy should be considered with chondrodysplasia.