Two novel mutations in PADI6 and TLE6 genes cause female infertility due to arrest in embryonic development

Purpose This study aims to identify genetic causes of female infertility associated with recurrent failure of assisted reproductive technology (ART) characterized by embryonic developmental arrest. Methods We recruited infertile patients from two consanguineous families from the Reproductive Medicine Center of Guizhou Provincial People’s Hospital. Peripheral blood was collected for genomic DNA extraction. Two affected individuals and their family members were performed with whole-exome sequencing and Sanger validation in order to identify possible causative genes. For further analyzing the effect of splicing mutation on mRNA integrity in vivo, TLE6 cDNA from the peripheral blood lymphocyte of the affected individual was sequenced. In addition, the possible impact of the pathogenic mutation on the structure and function of the protein were also assessed. Results Two novel homozygous mutations in the peptidylarginine deiminase type VI ( PADI6 ) and the transducin-like enhancer of split 6 ( TLE6 ) genes were identified in the two families. One patient carried the frameshift deletion mutation c.831_832del:p.S278Pfs * 59 of the PADI6 gene and the other patient carried the splicing mutation c.1245-2 A>G of the TLE6 gene. The analysis of the mRNA from the proband’s peripheral blood leukocytes confirmed aberrant splicing. Conclusions Our findings expand the mutational spectrum of PADI6 and TLE6 associated with embryonic developmental arrest and deepen our understanding of the genetic causes of infertility with recurrent ART failure.