Identification of the novel homozygous whole exon deletion in MEI1 underlying azoospermia and embryonic arrest in one consanguineous family.

This study characterized a male infertile patient suffering from azoospermia and a female infertile patient with embryonic arrest from one consanguineous family. We aimed to elucidate the novel pathogenic mechanism and provide support for the genetic diagnosis of infertility. Mutations were detected by whole-exome sequencing (WES) and confirmed by Sanger sequencing. Effect of the mutations on mRNA level was investigated by sequencing the cDNA amplification product. Functional characterization of the mutations was investigated through transfection in HEK293T cells in vitro, and the subcellular localization and protein levels were evaluated by immunofluorescence and western blot. Preimplantation genetic testing was performed to analyze chromosomal anomalies of the arrested embryos. The novel homozygous whole exon deletion of exon 19 in MEI1 was detected by WES. Amplification and sequencing of the cDNA verified the deletion of whole exon of MEI1. Quantitative expression revealed that the deletion result in almost no detectable expression of MEI1 Exon 19 in patients, and their mother is a heterozygous carrier of this whole exon deletion. Western blotting revealed that the whole exon deletion in MEI1 result in production of truncated MEI1 protein, corresponding to the predicted premature termination at Exon 20 of MEI1. Highly chromosomal anomalies were revealed in arrested embryos with MEI1 mutation. Overall, this study reported the first exon rearrangement of MEI1, thus broadening the mutational pattern and spectrum of MEI1-associated infertility, and also revealed the aneuploidies of embryos with MEI1 mutation as a potential reason for declined developmental potency and embryonic arrest.