Whole exome sequencing revealed a heterozygous elongation factor Tu GTP-binding domain containing 2(EFTUD2)mutation in a couple experiencing recurrent pregnancy loss

To the Editor:Recurrent pregnancy loss(RPL)is defined as the failure of two or more clinically recognized pregnancies.[1]Both parental and embryonic/fetal factors are associated with RPL.Parental factors include balanced chromosome rearrangements,maternal antiphospholipid syndrome,uterine anomalies,and hormonal or metabolic disorders.[2]Of the examined products of conception(POC),approximately 60%of early pregnancy losses result from sporadic chromosomal abnormalities in embryos,specifically numeric chromosome errors.However,up to 50%of RPL cases remain unexplainable by known causes.Here,we report a couple who have experienced four consecutive clinical pregnancy losses within 10 weeks of gestation,and describe a novel(elongation factor Tu GTP-binding domain containing 2[EFTUD2],Online Mendelian Inheritance in Man[MIM]#603892)nonsense mutation(c.1012G>T,p.E338∗)found in embryonic tissues from each of the last three miscarriages by whole exome sequencing(WES)analysis.In addition,we generated a zebrafish line with a mutation homologous to the human EFTUD2 disruption to investigate the relationship between this mutation and RPL.We hypothesized that the mutation was associated with embryonic lethality,which may induce RPL in patients.The study was approved by the Medical Ethics Committee of the West China Second University Hospital,Sichuan University,China(No.2016[029]).Written informed consent was obtained from the couple before genetic testing.