Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice

Several different mutations in the proteome of centriole 1 centriolar protein B (POC1B) have been linked to cone dystrophy or cone-rod dystrophy (CORD). However, mutations in POC1B that are associated with both CORD and oligoasthenoteratozoospermia (OAT) have not been reported previously. Here, whole-exome sequencing was performed to identify a homozygous frameshift variant (c.151delG) in POC1B in the two brothers who had been diagnosed with both CORD and OAT from a consanguineous family. Transcript and protein analyses of biological samples from the two patients carrying the variant showed that POC1B protein is lost in sperm cells. The system CRISPR/Cas9 was utilized to create poc1b(c.151delG/c.151delG) knock-in (KI) mice. Notably, poc1b(c.151delG/c.151delG) KI male mice presented with OAT phenotype. Additionally, testicular histology and transmission electron microscopy analysis of the testes and sperm indicated that Poc1b mutation results in abnormal formation of acrosomes and flagella. Collectively, according to our experimental data on human volunteers and animal models, biallelic mutations in POC1B can cause OAT and CORD in mice and humans.

Automated summary

This study identified a new mutation (c.151delG) in the POC1B gene that is associated with both cone-rod dystrophy (CORD) and oligoasthenoteratozoospermia (OAT). The mutation results in loss of POC1B protein in sperm cells. Using CRISPR/Cas9 technology, the mutation was introduced into mice, which showed OAT phenotype and abnormal acrosome and flagella formation in sperm and testicular histology.