Novel DNAH17 mutations associated with fertilization failures after ICSI

Area of Science:

• Human Reproduction
• Genetics
• Male Infertility

Background:

• Fertilization is crucial for human reproduction, but male genetic factors causing total fertilization failure (TFF) remain largely unidentified.
• Mutations in PLCZ1 are the only previously reported male genetic cause of TFF.

Observation:

• A patient with primary infertility experienced TFF after two intracytoplasmic sperm injection (ICSI) cycles.
• Donor sperm use resulted in a successful pregnancy, indicating the issue was male-specific.
• Genetic analysis revealed compound heterozygous variants in the DNAH17 gene.

Findings:

• Identified compound heterozygous variants in DNAH17: c.1048 C>T (p.Arg350*) and c.3390G>A (p.Met1130Ile).
• The p.Met1130Ile variant is highly conserved across mammalian species, suggesting functional importance.
• These DNAH17 variants are associated with male infertility and TFF.

Implications:

• This discovery expands the spectrum of known genetic causes for male infertility and TFF.
• Highlights DNAH17 as a potential candidate gene for diagnosing male infertility.
• Further research into DNAH17 function could offer new insights into fertilization mechanisms.