Novel homozygous mutation in IQCN gene causes male infertility and fertilization failure in a consanguineous mating family.

Genetic factors play an important role in oocyte activation defects and fertilization failure. We identified one novel mutation in the IQ motif containing the N (IQCN) gene that possibly led to human fertilization failure. The whole exome sequencing and Sanger sequencing was conducted in the proband and his parents. Mutations were assessed after frequency screening of public exome databases, and the homozygous variants shared by the proband and his parents were selected. A new homozygous variant in the gene IQCN (HGNC: 29350, GenBank: NM_001145304.2, exon 3, c.2388G>A, p.Trp796Ter) was identified, which was rare compared with public databases. The variant was considered of unknown significance by online software prediction. The proband with this novel IQCN mutation failed to fertilize even with intracytoplasmic sperm injection (ICSI) or intracytoplasmic sperm injection-assisted oocyte activation (ICSI-AOA). Our findings expand the genetic and phenotypic spectrum of IQCN variants in causing male infertility, and the novel mutation in IQCN provides genetic evidence of fertilization failure.