Biallelic mutations in Sperm flagellum 2 cause human multiple morphological abnormalities of the sperm flagella...

Area of Science:

• Genetics
• Reproductive Biology
• Cell Biology

Background:

• Male infertility is a significant concern, with multiple morphological abnormalities of the sperm flagella (MMAF) being a key factor.
• The SPEF2 gene is known to play a role in sperm motility and flagellum structure, with mutations linked to sperm tail defects.

Purpose of the Study:

• To investigate the genetic basis of MMAF in an infertile male patient.
• To identify novel mutations in the SPEF2 gene and elucidate their impact on sperm structure and function.

Main Methods:

• Genetic analysis of an MMAF patient.
• Identification and confirmation of biallelic SPEF2 gene mutations using Sanger sequencing.
• In silico analysis to predict the pathogenicity of the identified variations.
• Assessment of SPEF2 protein expression in patient spermatozoa.
• Ultrastructural analysis of sperm axoneme and mitochondrial sheath defects.

Main Results:

• Novel biallelic mutations in the SPEF2 gene were identified in the MMAF patient.
• In silico analysis confirmed these variations as deleterious.
• Significantly reduced expression of truncated SPEF2 protein was observed in the patient's spermatozoa.
• Spermatozoa with these mutations exhibited severe ultrastructural defects in the axoneme and mitochondrial sheath.

Conclusions:

• Biallelic mutations in the SPEF2 gene are a potential cause of severe sperm flagellum defects in human MMAF.
• This study identifies SPEF2 as a novel candidate genetic pathogen for the MMAF phenotype.
• Findings contribute to understanding the genetic etiology of male infertility associated with sperm flagellum abnormalities.