Prenatal diagnosis and mutation analysis of fibroblast growth factor receptor 3 gene in achondroplasia

Objective To explore the value of prenatal genetical diagnosis by mutation analysis of achondroplasia (ACH) fibroblast growth factor receptor 3 (FGFR3) gene. Methods Genomic DNA from nine ACH patients and their parents in Gansu Maternal and Child Health Hospital from July, 2010 to December, 2014 was prepared for polymerase chain reaction. Direct sequencing revealed the samples were performed after amplification of exon 10 of FGFR3 containing the potential mutation. Fetal DNA was extracted from cells in both amniotic fluid and umbilical cord, and then exon 10 of FGFR3 was also tested. Three fetuses with short-limb dysplasia were also included and prenatal diagnosis was offered to them through amniocentesis or cordocentesis. Results Prenatal ultrasonography test showed shorter femoral length, which was less than 2-3 standard deviation of normal reference dysplasia fetal performance for femoral short. Femur length is lower than 2-3 standard deviation minus normal value, and discrepancy in biparietal diameter compared with fetuses at the same gestational age. In the four families with one ACH parent, c.1138G>A heterozygous mutation was detected in all of the four mothers, while two fetuses among them showed c.1138G>A heterozygous mutation mutation and the other two were normal. There were other two fetuses with c.1138G>A heterozygous mutation from other two families, one's father had c.1138G>A heterozygous mutations, but not the mother, the other had c.1138G>A heterozygous mutations in both the mother and father. Among the three families with unaffected parents but each had a de novo c.1138G>A mutation child, no mutation of c.1138G>A genotype was detected in their fetuses, neither in the three fetus with short limb dysplasia. Four fetuses with a c.1138G>A mutation and three with short-limb dysplasia were terminated. The other five fetuses whose genotype was normal were born and healthy with normal phenotype at one-year-old follow-up. Conclusion FGFR3genetic analysis could provide information for genetic counseling and prenatal diagnosis for ACH parents or parents who had an ACH baby to prevent birth defect. Key words: Achondroplasia; Prenatal diagnosis; Receptor, fibroblast growth factor, type 3