A novel mutation in PCD-associated gene DNAAF3 causes male infertility due to asthenozoospermia

Area of Science:

• Genetics
• Reproductive Medicine
• Cell Biology

Background:

• Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive disorder characterized by respiratory infections and infertility.
• The DNAAF3 gene has been linked to PCD, with various mutations causing diverse clinical presentations.
• Sperm defects in males with PCD, particularly those with DNAAF3 mutations, remain under-investigated.

Purpose of the Study:

• To investigate the sperm phenotype in a patient with primary ciliary dyskinesia and infertility.
• To identify the genetic cause of the patient's condition and its impact on sperm function.
• To expand the understanding of DNAAF3 mutations and their role in male infertility.

Main Methods:

• Whole-exome sequencing and Sanger sequencing to identify DNA mutations.
• Transmission electron microscopy and immunostaining to analyze sperm ultrastructure and protein composition.
• Clinical evaluation including assessment of respiratory and reproductive health.

Main Results:

• A novel homozygous mutation in DNAAF3 (c.551T>A; p.V184E) was identified in the PCD patient.
• Sperm analysis revealed a complete absence of outer dynein arms and partial absence of inner dynein arms, leading to reduced motility (severe asthenozoospermia).
• The patient's infertility was successfully treated with intracytoplasmic sperm injection (ICSI), resulting in a successful pregnancy.

Conclusions:

• Pathogenic mutations in DNAAF3 can cause severe asthenozoospermia and male infertility in humans due to defects in sperm flagella axoneme.
• This study enhances the understanding of sperm characteristics in patients with DNAAF3 mutations.
• The findings contribute to the genetic diagnosis and potential therapeutic strategies for infertile patients with PCD.