Biallelic Recessive Mutations in <i>TLE6</i> and <i>NLRP5</i> Cause Female Infertility Characterized by Human Early Embryonic Arrest.

ABSTRACT: Preimplantation embryonic developmental arrest (EDA) is a common cause of unexplained female infertility. Genetic factors are believed to be one of the primary causes contributing to EDA. In this study, we identify four novel compound heterozygous mutations in TLE6 and NLRP5, in two infertile female patients experiencing recurrent EDA, using whole-exome sequencing. Functional analysis revealed that the two splicing mutations in TLE6 (c.541+2dupT) and NLRP5 (c.2957+4A>G) resulted in aberrant RNA splicing, leading to abnormal truncations of the corresponding proteins. In vitro experiments further validated that a missense mutation in NLRP5 led to increased mRNA and protein expression levels compared to wild type, when transfected into HEK293T cells.

SUBMITTER: Li R 

PROVIDER: S-EPMC11919057 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature