A novel CFAP57 nonsense mutation causes asthenozoospermia in a consanguineous Emirati family
Abdelaziz Tlili1,2, Ahlam Kaddoura3, Jihen Chouchen4
1Department of Applied Biology, College of Sciences, University of Sharjah, Building W8 - Room 107, 27272, Sharjah, United Arab Emirates. atlili@sharjah.ac.ae.
Background:
CFAP57 is essential for the development and function of sperm flagella, as it is required for the assembly and stability of the inner dynein arm (IDA) that drive sperm motility. Mutations in CFAP57 have been associated with multiple morphological abnormalities of the sperm flagella (MMAF), a leading cause of male infertility. Both human and mouse studies have shown that the loss of CFAP57 protein disrupts IDA assembly, impairing sperm motility. However, the genetic causes remain unknown in many MMAF cases, highlighting the importance of identifying additional mutations.
Materials And Methods:
In this study, we examined a consanguineous Emirati family with a male patient clinically diagnosed with asthenozoospermia. Semen analysis revealed abnormalities in sperm motility and morphology. Saliva and peripheral blood samples were collected, from which genomic DNA was extracted and subjected to whole-exome sequencing (WES). Sanger sequencing was performed to confirm the segregation of candidate variants within the family.
Results:
WES revealed a novel homozygous nonsense mutation in CFAP57 (c.3223 C > T; p.Arg1075Ter), located within a large homozygous region on chromosome 1. Sanger sequencing confirmed the segregation of the variant within the family; the proband was homozygous for the mutation, while both parents were heterozygous carriers. Semen analysis showed that 63% of sperm were immotile and only 4% had normal morphology, consistent with an MMAF phenotype. Notably, the patient exhibited no signs of primary ciliary dyskinesia (PCD), suggesting that the mutation selectively affects the sperm-specific isoform of CFAP57.
Discussion:
This study identifies a novel CFAP57 mutation associated with MMAF, expanding the mutational spectrum of the gene and supporting its potential role in male infertility, which warrants further investigation in larger cohorts.
Insights
A novel CFAP57 gene mutation was identified in an Emirati family, causing multiple morphological abnormalities of the sperm flagella (MMAF) and male infertility. This finding expands the known genetic causes of infertility.
Area of Science:
- Genetics
- Reproductive Biology
- Human Molecular Genetics
Background:
- CFAP57 is crucial for sperm flagella development and function, specifically for inner dynein arm assembly and stability.
- Mutations in CFAP57 are linked to multiple morphological abnormalities of the sperm flagella (MMAF), a primary cause of male infertility.
- Previous studies show CFAP57 loss impairs sperm motility, but genetic causes for many MMAF cases remain unidentified.
Purpose of the Study:
- To identify the genetic basis of asthenozoospermia in a consanguineous Emirati family.
- To investigate the role of CFAP57 mutations in male infertility and MMAF.
Main Methods:
- Whole-exome sequencing (WES) was performed on genomic DNA from an affected patient and family members.
- Sanger sequencing was used to confirm the segregation of identified variants within the family.
- Semen analysis was conducted to assess sperm motility and morphology.
Main Results:
- A novel homozygous nonsense mutation (c.3223 C>T; p.Arg1075Ter) in the CFAP57 gene was identified in the proband.
- The mutation segregated within the family, with parents being heterozygous carriers.
- The patient presented with severe asthenozoospermia and abnormal sperm morphology, consistent with MMAF, but without signs of primary ciliary dyskinesia (PCD).
Conclusions:
- A novel CFAP57 mutation is associated with MMAF and male infertility.
- This discovery broadens the spectrum of CFAP57 mutations linked to infertility.
- Further research in larger populations is warranted to confirm the role of CFAP57 in male infertility.
Related Concept Videos
01:23Infertility in Males
01:31Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
01:43Sex-linked Disorders
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:39Mutations