A novel variant in TLE6 is associated with embryonic developmental arrest (EDA) in familial female infertility

This study aims to identify genetic causes of familial female infertility characterized by embryonic developmental arrest (EDA) and repeated implantation failure (RIF) with oocyte donation IVF cycle. We used Whole-exome sequencing and Sanger validation to find causative genes in an Iranian consanguineous family that had 3 infertile daughters, 4 fertile daughters, and 2 fertile sons. All patients in this consanguineous family exhibited typical manifestations of unexplained RIF and EDA. Genetic analysis identified a homozygous missense variant (c.G1054C:p.G352R) in exon 13 of the TLE6 gene that cosegregated with the EDA phenotype in an autosomal recessive pattern. Other members of the family, the gene carriers, remain clinically asymptomatic and fertile. Our findings identify a novel nonsynonymous variant, c.G1054C:p.G352R, in the TLE6 gene within a consanguineous Iranian family with autosomal-recessive female infertility and broaden the genetic spectrum of TLE6-associated EDA.