Clinical exome sequencing identifies novel compound heterozygous mutations of the 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 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 mutations, which promotes the prognostic value of testing for mutations in infertile women with fertilization failure.