Clinical exome sequencing identifies novel compound heterozygous mutations of the WEE2 gene in primary infertile women with fertilization failure

Objective: The genetic basis of fertilization failure after intracytoplasmic sperm injection (ICSI) is largely unknown and the aim of this study is to investigate the genetic causes of fertilization failure in primary infertile women. Methods: Six affected women diagnosed with infertility and fertilization failure were recruited. The genetically pathogenic factor of their fertilization failures were investigated by clinical exome sequencing. One hundred healthy controls were verified by Sanger sequencing. Results: Novel compound heterozygous mutations c.625G> T and c.759-2A> G of WEE2 in one affected individual were revealed by clinical exome sequencing. Trios analysis of the mutations represented an autosomal recessive pattern. The nonsense mutation c.625G> T (p.Glu209*) indicated the truncation of the WEE2 protein and c.759-2A> G was predicted to affect the splicing. Conclusions: The novel variants extend the spectrum of WEE2 mutations, which promotes the prognostic value of testing for WEE2 mutations in infertile women with fertilization failure.